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Existing biosimilars are safe, effective alternatives to their reference biologics, and are increasingly being incorporated into oncology treatment guidelines. Technological advances that have emerged in the years since biologic agents entered the market allow for the careful assessment of “critical clinical attributes” of biosimilar agents. This helps ensure the safety and efficacy of biosimilars, as well as their structural, functional, and behavioral similarities to the original reference biologics, according to Gary Lyman MD, MPH, professor and senior lead, health care quality and policy at the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center, Seattle. Biosimilars are increasingly being included as acceptable alternatives in treatment guidelines, and in this episode Dr. Lyman discussed the reasons why they are considered safe and effective, how they can add value for oncology patients, and the need for ongoing diligence in monitoring their effects. Biosimilars in oncology – key points: The developers of biosimilar agents must prove biosimilarity to the reference agent, and generally go through “many of the same, if not all, preclinical steps.” Regulatory requirements are sufficient to ensure there are no clinically meaningful differences in the safety, purity, strength, and efficacy of biosimilars. Unlike the originator biologics, biosimilars aren’t typically required to complete multiple costly phase 3 clinical studies that drive up drug costs. This has the potential to rein in drug prices for biologics, which have revolutionized oncology and many other fields – but at a significant price. There has been some progress with respect to biologic cost reductions in the wake of biosimilar approvals, but the cost effects of biosimilars for newer reference agents will take time to emerge. Further prolonging the cost-reducing effects of biosimilar availability is the fact that early biosimilars were mainly used for supportive care whereas newer biosimilars are more often used for curative intent, which may lead to slower uptake due to hesitancy among clinicians and patients. The European Medicines Agency (EMA) is about a decade ahead of the United States when it comes to approvals and acceptance of biosimilars. Of note, no approved biosimilar has been removed from the market due to concerns about safety and efficacy. This is “a huge testament to the durability of biosimilars and the strength of the regulatory process,” Dr. Lyman said, noting that the EMA and FDA have similar processes when it comes to such approvals. “Drift,” the inevitable changes over time in an agent’s characteristics, can lead to changes in safety and efficacy. This means that diligence in monitoring effects and outcomes with both biologics and biosimilars is essential. Any concerns should be reported immediately and investigated. Show notes written by Sharon Worcester, MA, a reporter for MDedge and Medscape. Disclosures Dr. Henry has no relevant disclosures. Dr. Lyman disclosed relationships with Amgen, Jazz Pharmaceuticals, Partners Therapeutics, Sandoz, Seattle Genetics, Bristol Myers Squibb, BeyondSpring, Samsung, G1 Therapeutics, and Merck. * * * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

A “very basic” type of gene therapy could potentially cure hemophilia, but a major hurdle has been the lack of an effective mode of delivery. Recent strides in using adeno-associated virus (AAV) vectors are changing that, and Glenn Pierce, MD, World Federation of Hemophilia Vice President, Medical, predicts approvals in the next 12-18 months. Dr. Pierce shared his personal experience with hemophilia and discussed his and others’ ongoing research on the use of AAV-mediated gene therapy with host David Henry, MD, in this episode. Hemophilia and AAV gene therapy key points: Hemophilia is caused by a monogenic defect and could, theoretically, be cured by gene replacement or augmentation, says Dr. Pierce, who notes that “it sounds disarmingly simple, but behind that simplicity is a very complex procedure.” The approach uses “gene addition,” which is a basic gene therapy involving the addition of a normal gene to the variant in an individual. This ultimately corrects the clotting factor deficiency. The complexity is in getting the normal gene into the body where it can have the intended therapeutic effect. After more than 20 years of working to overcome that barrier, Dr. Pierce and others are finding success with using AAVs. The approach has some similarities to that used in developing the mRNA COVID-19 vaccines but requires the use of DNA established within the virus (rather than mRNA) to provide a more stable effect. Questions about how long it will last are currently being investigated. Multiple phase 3 trials are underway or completed. Data from two of those have been released in recent months, and the results are very encouraging: “It’s a remarkable achievement – many patients are doing well and, for all intents and purposes, could be considered free of [hemophilia],” Dr. Pierce says, adding that he would “potentially … use the ‘C word’ – cured – for at least a period of time.” The therapy is generally well tolerated. Efforts are ongoing to identify the best ways to proactively and reactively use prednisone to manage side effects such as mild increases in transaminase levels. To date, the risk-benefit profile appears reasonable for patients with clotting factor IX deficiency, and it is likely that the therapy in that setting “will march toward the regulatory process to determine if it’s safe and effective for approval,” he said. Responses in those with clotting factor VIII deficiency have been more variable, with some patients requiring long-term prednisone use, which is problematic. More information is needed about this, but investigation is ongoing, he said. Registries are available and many companies are involved in clinical trials. Clinicians and patients can look for information at clinicaltrials.gov, wfh.org (which publishes trial results and conducts workshops and meetings), and at the US National Hemophilia Foundation (Hemophilia.org) and the Society of Thrombosis and Hemostasis (ISTH.org). Show notes written by Sharon Worcester, MA, a reporter for MDedge and Medscape. Disclosures Dr. Henry has no relevant disclosures. Dr. Pierce disclosed relationships with Ambys Medicines, BioMarin, BridgeBio, CRISPR Therapeutics, Decibel Therapeutics, Frontera, Geneception, Generation Bio, Novo Nordisk, Pfizer, Regeneron, Third Rock Ventures, Voyager Therapeutics, Global Blood Therapeutics, VarmX SAB, the National Hemophilia Foundation Medical and Scientific Advisory Council, and the World Federation of Hemophilia. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd  

At least 17 cases of thrombosis and thrombocytopenia have been reported in patients who received the Johnson & Johnson COVID-19 vaccine in the United States. Such events have been reported in patients who received the AstraZeneca vaccine as well. In this episode, Adam C. Cuker, MD, of the University of Pennsylvania, Philadelphia, tells host David H. Henry, MD, how to identify and manage patients with these vaccine-induced events. What’s in a name? The phenomenon of vaccine-induced thrombosis and thrombocytopenia has been given different names, including: Vaccine-induced immune thrombotic thrombocytopenia (VITT) Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) Thrombosis and thrombocytopenia syndrome (TTS). Dr. Cuker’s preferred acronym is VITT. VITT is an immune-mediated reaction to the Johnson & Johnson and AstraZeneca vaccines that “results in thrombocytopenia and a strong propensity for thrombosis,” Dr. Cuker explained. Dr. Henry noted that VITT is reminiscent of heparin-induced thrombocytopenia (HIT). Incidence unclear VITT appears to be “very rare,” but “we still don't have a great sense of how common it is” because additional cases may not have been recognized or have yet to present, Dr. Cuker said. VITT occurs about 5-30 days after vaccination. VITT appears to be mediated by IgG antibodies, which take time to build up. The exact mechanism is unknown, but VITT could be related to the adenovirus vector used in the Johnson & Johnson and AstraZeneca vaccines, Dr. Cuker said. The first 15 cases of VITT associated with the Johnson & Johnson vaccine occurred in women, and most patients were aged under 50 years. In Canada, where the AstraZeneca vaccine is available, cases of VITT have been reported in patients in their 80s and 90s. Diagnosing VITT Symptoms of VITT can include severe, unrelenting headache; severe abdominal pain; nausea and vomiting; as well as typical signs and symptoms of deep vein thrombosis or pulmonary embolism. To determine if a patient has VITT, Dr. Cuker recommends ordering a disseminated intravascular coagulation panel – prothrombin time, partial thromboplastin time, fibrinogen, and D-dimer – as well as a standard HIT enzyme-linked immunosorbent assay (ELISA). Rapid immunoassays for HIT are not reliable for VITT, so HIT ELISA must be used, Dr. Cuker emphasized. Most patients with VITT have a “strongly positive” ELISA with optical density values “well in excess of 100 or 1.0,” depending on the scale, Dr. Cuker said. Manage VITT like HIT Patients should receive an anticoagulant, but not heparin, Dr. Cuker said. It isn’t clear if heparin will be harmful in patients with VITT, but current guidelines recommend avoiding heparin. He also advised against using warfarin or vitamin K antagonists in patients with VITT “at least until their platelet count recovers.” High-dose intravenous immunoglobulin (e.g., 1 g/kg for 2 consecutive days) is recommended, as it is believed to interfere with platelet activation. Show notes written by M. Alexander Otto, a reporter for MDedge and Medscape. Disclosures Dr. Henry has no relevant disclosures. Dr. Cuker has served as a consultant for Synergy Pharmaceuticals; has received authorship royalties from UpToDate; and his institution has received research support on his behalf from Alexion, Bayer, Novartis, Novo Nordisk, Pfizer, Sanofi, Spark Therapeutics, and Takeda. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Craig Chepke, MD, speaks with Lorenzo Norris, MD, about changes he made to his practice during the COVID-19 pandemic, and plans to make some of those changes permanent. Dr. Chepke is a psychiatrist in Huntersville, N.C., and adjunct associate professor at Atrium Health and adjunct assistant professor at the University of North Carolina at Chapel Hill. He disclosed serving as a consultant and speaker for Otsuka and Janssen, and as a speaker for Alkermes. Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures. Take-home points Dr. Chepke discussed his strategies for adapting his practice to the restrictions of the pandemic. He engaged in shared decision-making with patients when modifying his practice, including starting a drive-through pharmacotherapy clinic. To ensure that patients continued to have access to treatments such as long-acting injectable antipsychotics and esketamine, Dr. Chepke created a system in which patients could drive up to his clinic to have the medication administered. Because esketamine requires a 2-hour monitoring period after administration, he adapted the safety protocol. After patients received their intranasal spray dosage, they would complete the monitoring period in their car in the parking lot outside of his office, which was close enough to the clinic for Dr. Chepke to physically observe the patient, and to monitor vital signs wirelessly via a Bluetooth-enabled blood pressure cuff. Throughout the pandemic, Dr. Chepke found ways to care for his patients’ physical and mental health. He also adopted technologies that help him monitor his patients' vital signs and glucose levels. Especially while focusing on treatment-resistant psychiatric illness, Dr. Chepke invites family members to participate in evaluation and treatment. He uses this approach because he realizes that effective treatment must involve the system in which the individual exists. Dr. Chepke and Dr. Norris discussed ways in which clinicians can extend hope to their patients through flexibility and innovation, especially throughout the pandemic. Providing hope to patients demonstrates belief in a better future. Reference Chepke C. Current Psychiatry. 2020 May;19(5):29-30. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com  

The combined clinical cell-cycle risk (CCR) score uses clinical and genetic factors to assess the risk of metastasis after radiation therapy in patients with prostate cancer. The CCR score has proven accurate in studies and can guide post-radiation treatment decisions in practice, according to Jonathan D. Tward, MD, PhD, of the University of Utah, Salt Lake City. Dr. Tward discusses the CCR score with host David Henry, MD, in this episode. About the score The CCR score combines the cell-cycle progression (CCP) score (available commercially as the Prolaris test) and the Cancer of the Prostate Risk Assessment (CAPRA) score to more precisely determine the postradiation risk for metastatic disease. Investigators identified a threshold for determining precise risk levels (2.112), which allows for personalized treatment decision-making based on more individual characteristics than standard risk-group categorizations, according to Dr. Tward. He noted that standard risk groups can include a broad range of actual risk even within a given category. Risk groups are “reasonably good at prognosticating who may or may not go on to have metastasis etc., but they’re not that good,” Dr. Tward said. CCR score proves effective Dr. Tward and colleagues evaluated the CCR score in a retrospective study published in Clinical Genitourinary Cancer (https://bit.ly/3vlgUwe). The study included 718 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy. Results showed that patients with CCR scores below the identified threshold (2.112) could safely forgo multimodality therapy. CCR score bests other scoring systems In another study, the CCR score proved more accurate than other scoring systems. Dr. Tward presented findings from this study at the 2021 Genitourinary Cancers Symposium (https://bit.ly/3eBvAjM). The study included 741 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy. The CCR score predicted metastasis (hazard ratio, 2.21; C-index, 0.78) and did so better than National Comprehensive Cancer Network risk groups (C-index, 0.70), the CAPRA score alone (C-index, 0.71), or the CCP score alone (C-index, 0.69). Dr. Tward said he has used the CCR score in his own practice for years and found it helpful. Show notes written by Sharon Worcester, a reporter for MDedge and Medscape. Disclosures Both studies were funded by Myriad Genetics, the company that developed the Prolaris test. Dr. Tward disclosed relationships with Myriad Genetics and other companies. Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd 

John “Jack” Rozel, MD, MSL, returns to the Psychcast to talk with Lorenzo Norris, MD, about American gun violence and steps clinicians can take to disrupt it. Dr. Rozel is medical director of the resolve Crisis Network. He also serves as associate professor of psychiatry and adjunct professor of law at the University of Pittsburgh. Dr. Rozel is also past president of the American Association for Emergency Psychiatry. He has no disclosures. Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures. Take-home points Mass violence with guns is occurring with greater frequency and severity in the United States, compared with other countries. Mass shootings have been on the rise. In 2020 there were nearly 200 more mass shootings, compared with 2019. The United States has a broad swath of firearm violence: Deaths by suicide account 60% of gun deaths, and the remaining 40% are deaths by homicide. Only 1%-2% of firearm homicides are completed in mass shootings – which are defined as an event in which four or more people are shot in an indiscriminate manner. It is also a distinctly American problem that we have so many guns in our country. The United States has more civilian-held firearms (393 million) than the next 39 countries combined. Being an adult in the United States means being 25 times more likely to be the victim of a firearm homicide, compared with adults in any other country. Dr. Norris and Dr. Rozel conclude that violence assessments must always cover suicide and homicide risk because they are related types of violence, especially when it comes to guns. Summary Suicide risk is increased by 100-fold when a new gun enters the home, and the risk peaks in the first days to weeks of ownership and then trails off. However, there is a measurable difference in risk of suicide in the 5 years after the purchase. Dr. Rozel emphasizes that it is essential to ask patients about acquisition of new guns, because as circumstances change as with the pandemic, people may feel the need to buy a gun. Dr. Rozel presented a model for possibly reducing gun violence: Grievance: All violence starts with feeling like a victim; some people feel aggrieved after a disagreement or even a threat. The Pivot: This is a transition from simply having a grievance to violent ideation and wanting vengeance through violence. Perpetrators of violence shift from fantasy into research about planning and preparing to attack. Preparation: This stage includes acquiring weapons and, in some cases, tactical clothing. It also could include probing into their targets’ vulnerabilities, a “test attack,” and eventually the final attack. Breach: This entails a change in the safety of the potential victim.  Attack: This stage encompasses perpetrating the attack. Identifying a person at the grievance stage is the most effective place to intervene and potentially diffuse a violent situation by using motivational interviewing to enhance protective factors. Psychiatry’s greatest strength is meeting the aggressor where they are and hearing out the grievance. References Victor D and Taylor DB. A partial list of mass shootings in the United States in 2021. New York Times. 2021 Apr 16. Kim NY. Gun violence spiked during pandemic, even as the deadliest mass shootings waned. Poynter.org. 2021 Mar 25. Rozel JS and Mulvey EP. Annu Rev Clin Psychol. 2017 May 8;13:445-69. Metzl JM et al. Har Rev Psychiatry. 2021 Jan-Feb 01;29(1):81-9. Firearm access is a risk factor for suicide. Harvard School of Public Health. National Council for Behavioral Health. Mass Violence in America: Causes, impacts, and solutions. 2019 Aug. Gun Violence Archive *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Pediatric oncologists are used to dealing with emotional, heart-wrenching situations, but oncology took on a new dimension for Michael Weiner, MD, when both he and his daughter were diagnosed with cancer. Dr. Weiner, a pediatric oncologist at Columbia University, New York, describes his roles as oncologist, patient, and caregiver to host David H. Henry, MD, in this episode.  Oncologist as patient: Lessons learned Dr. Weiner’s journey as a cancer patient began when he felt a lymph node on his neck that he knew wasn’t “normal.” A colleague examined Dr. Weiner and suggested the “watch-and-wait” approach, but Dr. Weiner insisted on immediate biopsy. The diagnosis was follicular lymphoma, and Dr. Weiner had a hard time accepting that his malignancy was treatable but not curable. One of the things Dr. Weiner learned as a cancer patient is that “you really need to connect with your doctor,” so he chose a doctor who felt like a good fit for him. Another lesson Dr. Weiner learned was that cancer can be very isolating. Though friends and family can offer help and support, “you take this journey alone,” he said. Dr. Weiner was treated with rituximab and radiation, which proved successful. It’s been 3 years since he completed his treatment. Dr. Weiner had been reluctant to undergo radiation because of the risk of thyroid cancer, and, unfortunately, he now has a small thyroid nodule that’s under observation. Update: After this episode was recorded, Dr. Weiner was diagnosed with papillary thyroid cancer. He is set to undergo a total thyroidectomy. Oncologist as caregiver: Taking a backseat Dr. Weiner’s daughter was diagnosed with papillary thyroid carcinoma after a nodule was found on a routine exam. Dr. Weiner and his daughter decided to educate themselves about her malignancy and opted for an aggressive course of treatment. “I tried very, very hard to be a parent and not a physician,” Dr. Weiner said. He decided to put his faith in her care team. “I in no way participated in the final decision-making,” he said. His daughter ultimately had a total thyroidectomy and high-dose radioactive iodine. The process, like his own cancer journey, was difficult. Dr. Weiner recounts these experiences in his book “Living Cancer: Stories from an Oncologist, Father, and Survivor,” which can be found here: https://bit.ly/3n7TB5Z. Show notes written by M. Alexander Otto, a reporter for MDedge and Medscape. Disclosures Dr. Weiner and Dr. Henry have no relevant disclosures. These show notes were updated on 4/22. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Omar Sultan Haque, MD, PhD, talks with Lorenzo Norris, MD, about the need for medical schools to become responsive to physicians, medical students, and residents with mental disabilities. Dr. Haque is a physician, social scientist, and philosopher who is affiliated with the department of global health and social medicine at Harvard Medical School, Boston. He disclosed founding Dignity Brain Health, a clinic that seeks to provide clinical care for patients struggling with major depressive disorder. Dr. Haque also serves as medical director of Dignity Brain Health. Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures. Take-home points Dr. Haque and colleagues recently published a perspective piece in the New England Journal of Medicine about the “double stigma” against mental disabilities, which the authors define as “psychiatric, psychological, learning, and developmental disorders that impair functioning,” including common diagnoses, such as attention deficit disorder and major depressive disorder. Physicians and physicians-in-training, such as students and residents, face major challenges in disclosing mental disabilities, from fear of discrimination during the admissions process to stigma throughout training and licensure. Medical leave is often the only suggested solution to an exacerbation of a disability, and this response is likely to instill fear in trainees, because taking leave will require future disclosure and worsen the double stigma. Reasonable accommodations could improve functioning and allow trainees to remain enrolled and on their desired academic path. Dr. Haque recommends that medical schools and training programs have trained disability service providers (DSP) with specialized understanding of medical education and curricula who do not have conflicts of interest – as sometimes happens when they participate in other roles, such as serving as deans or professors within a medical school. A continued challenge to disability disclosures are questions on medical licensing applications and renewals about past or current diagnoses or treatment for mental disabilities. Dr. Haque reminds listeners that, according to the American Disabilities Act, these questions about past and current diagnoses are illegal if the answers to those questions do not affect physicians’ current functioning. Summary   Dr. Haque’s article offers several recommendations for medical schools, training programs, and licensing boards aimed at addressing the burden of the double stigma against mental disabilities within the culture of medical training and practice. Medical schools should clearly communicate that applicants with disabilities are welcome as part of a larger commitment to diversity, and individuals with mental disabilities should be admitted and allowed to complete training. Universities should hire medical school–specific disability service providers who understand medical education and are committed to parity for individuals with physical and mental disabilities. Policies related to mental disabilities should be clearly publicized so that students and trainees know what to expect if they disclose a disability, and should create reasonable accommodations for those with mental disabilities instead of promoting medical leave as the only option. Faculty members and administrators could publicly describe their own protected time for therapy and highlight the professional successes of people who were able to disclose their condition and get reasonable accommodations. The Federation of State Medical Boards should enforce the ADA-based legal standard that questions about mental disabilities should be asked and answered only if they address current functional impairments that affect a physician’s ability to practice medicine safely. References Haque OS et al. N Engl J Med. 2021 Mar 11;384:888-9. Wimsatt LA et al. Am J Prevent Med. 2015 Nov. 49(5):703-14. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Studies have shown that chimeric antigen receptor (CAR) T-cell therapies produce responses in patients with relapsed/refractory B-cell lymphomas, but researchers continue to look for ways to improve efficacy, decrease toxicity, and overcome treatment resistance. Leslie Kean, MD, PhD, of Boston Children’s Hospital, discusses some of this research with host David H. Henry, MD, in this episode. Dr. Kean outlines four recent studies of CAR T-cell therapies in lymphoma. The studies were selected as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology. Primary Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma This study was designed to assess the efficacy and safety of axicabtagene ciloleucel (axi-cel) in patients with indolent lymphomas. In follicular lymphoma, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 80%. In marginal zone lymphoma, the ORR was 85%, and the CR rate was 60%. There was one grade 5 and one grade 4 case of cytokine release syndrome (CRS). Dr. Kean noted that 146 patients were evaluable for adverse events, so the single death related to CRS should be viewed in that context. Overall, 82% of patients had CRS of any grade. Jacobson C et al. ASH 2020, Abstract 700. https://bit.ly/32at91V. What’s involved in a CAR T-cell study? Dr. Kean explained that a patient is first deemed eligible by an oncologist and then enrolled in a CAR T-cell study. For studies like ZUMA-5 that are testing autologous CAR T cells, basic lab work is done to ensure the patient has a high enough lymphocyte count. The patient then undergoes apheresis, and the patient’s T cells are used to create the CAR T-cell product. The company developing the product transduces the T cells with the CAR so the resulting CAR T cells will target cancer cells. The therapy in ZUMA-5, axi-cel, targets CD19, which is expressed on B-cell lymphoma cells. Normal B cells express CD19 as well, so immunoglobulin replacement is sometimes necessary to offset the loss of normal B cells. Efficacy and Safety of Tisagenlecleucel in Adult Patients with Relapsed/Refractory Follicular Lymphoma: Interim Analysis of the Phase 2 ELARA Trial Tisagenlecleucel differs from axi-cel in the signaling domain, though tisagenlecleucel targets CD19 as well, Dr. Kean explained. She noted that tisagenlecleucel is a bit more long-lived than axi-cel. In this trial, tisagenlecleucel produced an ORR of 82% and a CR rate of 65%. There were no cases of grade 3 or higher CRS, which may be attributed to the different signaling domain, Dr. Kean said. Fowler NH et al. ASH 2020, Abstract 1149. https://bit.ly/2OIGjjA. TRANSCEND CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination with Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Patients in this study received the CAR T-cell therapy liso-cel in combination with the BTK inhibitor ibrutinib. The combination increased both efficacy and safety, as ibrutinib assisted in calming down the immune response. There were no grade 5 adverse events and no cases of grade 4 CRS or neurotoxicity. The ORR was 95%, and the CR rate was 63%. There was no difference in response among patients who had or had not received a BTK inhibitor previously, Dr. Kean noted. Wierda WG et al. ASH 2020, Abstract 544. https://bit.ly/3uPuJ5U. CD58 Aberrations Limit Durable Responses to CD19 CAR in Large B Cell Lymphoma Patients Treated with Axicabtagene Ciloleucel But Can Be Overcome Through Novel CAR Engineering Dr. Kean noted that CAR T-cell therapy typically produces a CR in more than 90% of patients within 30 days, but the long-term duration of response is about 50%. With this study, researchers wanted to investigate why a CAR T-cell therapy would fail and determine if any tumor-specific factors affect the duration of response. The team found that patients who had mutations in CD58 were less likely to achieve a CR to axi-cel, and most patients with these mutations ultimately progressed. CD2, the T-cell ligand for CD58, plays adhesive and costimulatory roles in T cells, and CAR T cells rely on intrinsic T-cell signaling to work, Dr. Kean explained. So if the CD2 in a CAR T cell can’t “see” CD58 on the tumor because of a mutation, the CAR T cell doesn’t work, she added. To bypass this, the researchers created a construct integrating CD2 costimulatory domains within the CAR molecule so it expressed CD2 in a way that doesn’t require CD58. The new construct “cures tumors like gangbusters” in mouse models, Dr. Kean said, adding that this CAR T-cell therapy could be coming to the clinic soon. Maizner RG et al. ASH 2020, Abstract 556. https://bit.ly/3283zL0. Looking ahead: Concerns about cost Cost is a critical barrier to receiving CAR T-cell therapy, Dr. Kean noted, especially for patients who require additional treatment after receiving CAR T cells. The next generation of CAR T-cell research should determine if this treatment is best used as a bridge to transplant or if CAR T-cell therapy can stand alone, she added. To make the cost more palatable, CAR T-cell products should be a final cure, Dr. Kean said. Show notes written by Malika Gill, MD, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Henry has no relevant disclosures. Dr. Kean disclosed relationships with Magenta Therapeutics, Bristol-Myers Squibb, Kymab, HiFiBiO Therapeutics, Regeneron, Novartis, Gilead, Bluebird Bio, and Forty Seven. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Géraldine Fauville, PhD, joins Lorenzo Norris, MD, to discuss some of the causes of Zoom fatigue and strategies that can make videoconferences productive. Dr. Fauville is the lead researcher on the Zoom Exhaustion & Fatigue Scale project. She also is assistant professor in the department of education, communication, and learning at the University of Gothenburg (Sweden). Dr. Fauville has no disclosures. Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures. Take-home points Dr. Fauville started her research on Zoom fatigue in the Virtual Human Interaction Lab at Stanford (Calif.) University, founded by Jeremy N. Bailenson, PhD. The lab has pioneered research on the common but poorly understood phenomenon of Zoom fatigue.  Videoconferencing, often through Zoom, has allowed people to connect throughout the pandemic, but there are features of this modality that can contribute to stress, and for many, social anxiety. Dr. Fauville and Dr. Norris discuss Zoom fatigue and which dynamics of videoconferencing contribute to a sense of anxiety, fatigue, and affect our general wellness in a society that has come to rely on videoconferencing as a primary form of communication and central to parts of our economy during the pandemic.  Dr. Fauville discusses how the size of faces on the screen and feeling observed activate anxiety and stress. Constant mirroring from seeing yourself reflected from the camera onto a screen can lead to self-judgment and negative emotions. Loss of traditional nonverbal communication and being forced to pay attention to verbal cues or exaggerate gestures can increase the cognitive load associated with conversations that occur via videoconference. Videoconferencing also restricts mobility, because people feel tethered to a small area within their camera’s view where they can be seen.  Summary During an in-person meeting, people will stare at you while you’re speaking, but on videoconferencing it can feel as if all eyes are on you the whole time, which contributes to stress and social anxiety.  Dr. Fauville discusses the “large face” dynamic; if these conferences were real-life interactions, it would be like having a very large face just a few inches from ours,  which can feel like an invasion of privacy. For the brain, having a face in close proximity to yours signals either a desire for intimacy or conflict.  Recommendation: Minimize the videoconferencing application as much as possible and keep the size of the faces smaller.  Zoom and other platforms lead to “constant mirroring.” Seeing our own image can result in persistent self-evaluation and judgment, which can contribute to anxiety and negative emotions.  Recommendation: Keep your camera on but hide self-view; doing so can combat this constant mirroring. Videoconferencing has severely limited mobility during meetings, which make people feel trapped in the view of the camera.  Recommendation: Using a standing desk allows for more freedom from the view of the camera. You can stretch your legs, walk around in the view of the camera, and create distance, especially if you have an external keyboard.  Nonverbal communication and behaviors are essential cues between humans. Videoconferencing that focuses on head and shoulders diminishes a large portion of body language. Videoconferences are more taxing for the brain than audio-only communication because people have to be even more in tune to the cues in speakers' verbal tones, and some nonverbal cues, such as nodding, become exaggerated.  Recommendation: Organizations should create guidelines aimed at mitigating Zoom fatigue. Suggestions include allowing people to turn off their cameras for portions of meetings or didactics, having a mix of audio/telephone and video meetings, and assessing whether the information from some meetings can included in email messages or shared documents.  Dr. Fauville and colleagues created the Zoom Exhaustion & Fatigue Scale (ZEF Scale) to quantify the phenomenon. Fifteen items on the scale focus on five dimensions of Zoom fatigue, such as general, visual, emotional, social, and motivational fatigue.  Part of the evaluation of Zoom fatigue should include examining how many videoconferences you have per day, the amount of time between each, and how long the conferences last.  References Ramachandran V. Stanford researchers identify four causes for ‘Zoom fatigue’ and their simple fixes. Stanford News. 2020 Feb 23. Fauville G et al. Zoom Exhaustion & Fatigue Scale. SSRN.com. 2021 Feb 23. Bailenson JN. Nonverbal overload: A theoretical argument for the causes of Zoom fatigue. Technology, Mind & Behavior. 2021 Feb 23;2(1). doi: 10.1037/tmb0000030. Zoom Exhaustion & Fatigue Scale survey: https://vhil.stanford.edu/zef/ *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Researchers have tracked the evolution of genetic germline testing in women with breast or ovarian cancer in recent years and reported the results in the Journal of Clinical Oncology. Study author Allison W. Kurian, MD, of Stanford (Calif.) University, describes the group’s findings (https://bit.ly/31RaSGR) to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode. Study rationale and methods Dr. Kurian said that an inflection point for breast cancer genetics was in 2013 when the U.S. Supreme Court ruled that gene patenting was not allowed for the purposes of genetic testing. As a result, the cost of testing BRCA1/2 genes fell, and testing became much more accessible. With their study, Dr. Kurian and colleagues aimed to look at trends following the increase in accessibility. The researchers used Surveillance, Epidemiology, and End Results Program (SEER) records of women aged 20 years and older who were diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia. The team linked these data to results of clinical germline testing through 2019. Dr. Kurian explained that the SEER data are comprehensive enough that all cancer cases in California and Georgia were likely included, the states provide a large catchment area of about 50 million people, and the states have different kinds of racial/ethnic diversity and urban/rural distribution. The researchers used the data to assess testing trends as well as rates of variants of uncertain significance (VUS) and pathogenic variants (PVs). Results by hypothesis Hypothesis 1: Multigene panels will entirely replace testing for BRCA1/2 only. This hypothesis was essentially correct. Testing of only two genes was almost totally replaced by testing many more genes. The number of genes tested for breast cancer increased annually by 28% over the study period. Hypothesis 2: Underutilization of testing patients with ovarian cancer will improve over time. It is standard of care to recommend genetic testing for all ovarian cancer patients. Based on 2013-2014 data, only one-third of women were tested. As tests became more accessible in subsequent years, the hope was that more women would be tested. Unfortunately, there was very little improvement in testing rates over the study period. Hypothesis 3: More patients will be tested at lower levels of pretest risk for PVs. In patients aged older than 60 years, testing rates increased for breast cancer (from 11% to 15%) and ovarian cancer (from 25% to 31%). Patients aged younger than 45 years had lower testing rates over time, however. Dr. Kurian noted that about 33% of ovarian cancer patients undergo genetic testing, but the goal is 100%. It is unclear if the goal should be 100% for breast cancer, Dr. Kurian said. Hypothesis 4: Sociodemographic difference in testing trends would not be seen. There was not much of a gap observed with breast cancer patients. For example, among patients with breast cancer, approximately 31% of those who had genetic testing were uninsured, 31% had Medicaid, and 26% had private insurance or Medicare. There is more of an equity issue with ovarian cancer. About 28% of those who had genetic testing were uninsured, 27% had Medicaid, and 39% had private insurance or Medicare. Dr. Kurian said disparities in ovarian cancer persist in patients who are uninsured and those in certain racial/ethnic groups, including African Americans. These patients are less likely to get genetic testing. Hypothesis 5: Detection of PVs and VUS will increase. The detection of VUS increased at a higher rate in comparison with PVs when more genes were being tested. This is likely because of the fact that, for every PV you find, you will find many more VUS, Dr. Kurian said. Hypothesis 6: Racial or ethnic disparities in rates of VUS will diminish over time. Disparities actually increased over the study period as more genes were tested. Some studies have suggested that VUS results lead to unnecessary prophylactic surgery, Dr. Kurian said. She added that the decision to undergo prophylactic surgery should not be based on a VUS because “the great majority of VUS turn out to be nothing.” Additional findings and implications for practice The study revealed that most PVs were in 20 genes associated with breast or ovarian cancer. Dr. Kurian and colleagues concluded that the way to improve testing is to focus on those 20 genes and ensure appropriate patients are being tested, rather than adding more genes to tests. Dr. Kurian said it is urgent to increase genetic testing in patients with ovarian cancer, as it is not being done at the rate it should be. Dr. Kurian also noted that one positive outcome of the COVID-19 pandemic has been an increase in telehealth visits and at-home genetic testing. Providing patients with these more convenient options could increase the use of genetic testing. Show notes written by Alesha Levenson, MD, a resident at Penn Medicine, Philadelphia. Disclosures Dr. Kurian disclosed relationships with Myriad Genetics, Ambry Genetics, Color Genomics, GeneDx/BioReference, InVitae, and Genentech. The study was supported by the National Cancer Institute, the Centers for Disease Control and Prevention, and the California Department of Public Health. Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights” (https://bit.ly/3m76xIP). He has no other conflicts of interest. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc Dr. Lyss on Twitter: @HeartlandOncDoc

Guest host Vicki L. Ellingrod, PharmD, talks with Kristen M. Ward, PharmD, and Amy Pasternak, PharmD, about integrating pharmacogenomic testing into psychiatric practice. Dr. Ellingrod is senior associate dean at the University of Michigan College of Pharmacy, Ann Arbor, and professor of psychiatry in the medical school. She is also section editor of the savvy psychopharmacology department in Current Psychiatry. Dr. Ellingrod has no relevant financial relationships to disclose. Dr. Ward and Dr. Pasternak are clinical assistant professors of pharmacy at the University of Michigan.  Dr. Ward and Dr. Pasternak report no relevant disclosures. Dr. Ward and Dr. Pasternak are team leads in the University of Michigan’s Precision Health Implementation Workgroup. Take-home points Pharmacogenomics is defined as the study of the relationship between genetic variations and how our body responds to medications. Two common reasons for ordering pharmacogenomic testing are that a patient or clinician wants testing completed before starting the trial of a psychotropic medication and that there are concerns about nonresponse or loss of response to medications. Common insurance criteria used to justify such testing include at least one failed medical trial; future use of a medication likely to be affected by genetic variants, such as metabolism through CYP2D6 or CYP2C19; or identification of human leukocyte antigen (HLA) variants before starting carbamazepine or oxcarbazepine. Quality improvement and usability campaigns around pharmacogenomic testing include ensuring that testing results are readily available in the medical record. Results should be searchable. Alerts can be created for prescribers when they order a medication for which a patient has a relevant genetic variant. After ordering testing, clinicians should document the patient’s medication response genotype and phenotype in the medical record so the information can be used for medications other than psychotropics. Summary Pharmacogenomic testing may be ordered for several reasons, including cases in which a patient or clinician wants information before switching to another medication or there are questions about failed medication trials. For approximately 50% of individuals who undergo pharmacogenomic testing, there may not be a change in treatment plans, or the results might not be conclusive enough to affect treatment. However, pharmacogenomic testing is useful in reassuring and improving adherence in patients who experience somatic adverse effects to psychotropic medications and want to know whether those effects are related to their metabolism. Getting insurance companies to cover pharmacogenetic testing can be tricky, and clinicians should be familiar with the criteria requested by insurers before ordering the tests. Many of the genetic-testing companies include a patient-assistance program to cover payment when insurance companies do not. In the medical record, it’s important to document the patient's genotype and phenotype. The patient’s genotype affects their metabolism of medications beyond psychotropics. Pharmacogenomic testing results can prevent serious adverse drug reactions. If testing comments on a patient’s carrier status for specific HLA subtypes implicated in drug metabolism, carbamazepine or other related medications should be added to the patient’s drug allergy list. States requirements about informed consent for genetic testing vary, so any clinicians who order such tests should be informed about their local laws. References Ellingrod VL. Current Psychiatry. 2019 Apr;18(4):29-33. Deardorff OG et al. Current Psychiatry. 2018 Jul;17(7):41-5. Ellingrod VL and Ward KM. Current Psychiatry. 2018 Jan;17(1):43-6. Bishop JR. Current Psychiatry. 2010 Sep;9(9):32-5. Maruf AA et al. Can J Psychiatry. 2020 Aug;65(8):521-30. National Institutes of Health. National Human Genome Research Institute. Genome Statute and Legislative Database. Clinical Pharmacogenetics Implementation Consortium. CPIC guidelines.. Pharmacogenetics Knowledge Base. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

A program called Drive By Flu-FIT has allowed for socially distanced colorectal cancer (CRC) screening during the COVID-19 pandemic. Armenta Washington, senior research coordinator at the University of Pennsylvania, describes the program to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode. What is Drive By Flu-FIT? Drive By Flu-FIT is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program. Flu-FIT was designed to increase access to CRC screening by offering take-home FIT tests to patients at the time of their annual flu shots. The goal of Drive By Flu-FIT is to provide a COVID-safe approach to CRC screening and counteract the decrease in CRC screening seen during the pandemic. Drive By Flu-FIT is a joint effort of the University of Pennsylvania, the Einstein Healthcare Network, Chi Eta Phi Sorority, and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region. How does Drive By Flu-FIT work? To participate in a Drive By Flu-FIT event, community members had to complete eligibility, registration, and demographic questionnaires online. Patients who were enrolled watched a short educational video on CRC and completed two questionnaires – one on CRC screening knowledge (14 items) and one on screening intentions (5 items) – before and after watching the video. At the Drive By Flu-FIT events, patients remained in their cars while physicians in personal protective equipment handed out FITs and explained how to use them and return them. Patients could also receive a flu vaccine at each event. Results: High return rate According to initial data, 335 patients registered for a Drive By Flu-FIT event, but 80 (23.9%) ultimately didn’t attend and 63 (18.8%) were found to be ineligible. A total of 192 patients attended and received a FIT (57.3%). Scores on both questionnaires increased after patients watched the educational video. Patients’ baseline knowledge of CRC was high but lacking in four areas: risk factors for CRC, the optimal frequency of FITs, the link between Lynch syndrome and CRC, and the relationship between physical activity and CRC risk. Of the 192 patients who received a FIT, 38 (19.7%) did not return it. There were 141 patients (73.4%) with a negative FIT result, while 13 (6.7%) had a positive FIT result and were referred for colonoscopy. Resources For more information on Flu-FIT, visit http://flufit.org/. For more details on Drive By Flu-FIT, see: AACR Virtual Meeting: COVID-19 and Cancer, Abstract S02-04: https://bit.ly/3szf0Hp. MDedge coverage of the meeting presentation: https://bit.ly/3szfrl1. Ms. Washington disclosed no conflicts of interest. The study was supported by the National Cancer Institute. The FITs were donated by Polymedco, and the flu vaccines were donated by the Philadelphia Public Health Department. Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights” (https://bit.ly/3m76xIP). He has no other conflicts of interest. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc Dr. Lyss on Twitter: @HeartlandOncDoc

Lorenzo Norris, MD, speaks with Tonya Cross Hansel, PhD, about processing incidents such as the Jan. 6, 2021, siege on the Capitol, and determining how to foster recovery. Dr. Hansel is an associate professor with the Tulane University School of Social Work in New Orleans. She has no conflicts of interest. Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures. Take-home points Dr. Hansel’s research focuses on measuring traumatic experiences and implementing systematic recovery initiatives that address negative symptoms by emphasizing individual and community strengths. The tendency to come together in times of vulnerability is a human instinct. The Jan. 6 Capitol siege was a traumatic and polarizing event; in a Pew survey 1 week later, 37% of respondents expressed a strong negative emotion in response to the riot. The unpreparedness of the U.S. Capitol Police and other law enforcement agencies led to fear and shock as much of the nation watched the breach unfold in real time on television. A variety of groups attended the protest. Some groups were involved in domestic terrorism, and others were part of political groups who came protest their grievances against the government. Those who attended the event with the intent of engaging in violence and instilling fear are considered domestic terrorists. Dr. Hansel said an event such as the insurrection wears on society by causing chronic stress, and one-time events such as the insurrection can lead to a prolonged state of anxiety. Terrorism and violence are sometimes triggered by disenfranchisement when violence seems like the only way to make one’s voice heard. Disasters with an economic fallout, such as natural disasters or the ongoing COVID-19 pandemic, can result in greater disenfranchisement. Prevention of future attacks and domestic terrorism must balance people’s ability to speak out and protest with an effort to avoid disenfranchisement. The way forward must also include addressing chronic fear. Dr. Hansel suggests that building community over shared values is a powerful way to foster resilience after disaster. In the pandemic, we have all experienced sacrifice and hardship. When society moves beyond survival mode, efforts must be made to connect over our shared sense of loss. References Hartig H. In their own words: How Americans reacted to the rioting at the U.S. Capitol. Pew Research Center. 2021 Jan 15. Pape RA and Ruby K. The Capitol rioters aren’t like other extremists. The Atlantic. 2021 Feb 2. Ellis BH et al. Studies in Conflict & Terrorism. 2019 May 31. doi: 10.1080/1057610X.2019.1616929. Hansel T et al. Traumatology. 2020;26(3):278-84. Saltzman LY et al. Curr Psychiatry Rep. 2017 Jun 19. doi: 10.1007/s/1920-017-0786-6. Hall BJ et al. PLoS One. 2015 Apr 24. doi 10.1371/journal.pone.0124782. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Earlier this year, clinical practice guidelines for the diagnosis and management of von Willebrand disease (VWD) were published in Blood Advances. The guidelines (https://bit.ly/2OIfKLE) are a collaborative effort from the American Society of Hematology, the International Society on Thrombosis and Haemostasis, the National Hemophilia Foundation, and the World Federation of Hemophilia. Guideline author Paula James, MD, of Queens University, Kingston, Ont., reviews some of the recommendations in these guidelines with host David H. Henry, MD, in this episode. Case discussion A patient presents with the complaint of heavy menstrual bleeding, which could indicate a bleeding disorder such as VWD. How does one diagnose or rule out VWD? Tests to order include CBC, prothrombin time (PT), and partial thromboplastin time (PTT). Results of CBC, PT, and PTT could be normal, which would necessitate special testing to specifically look at factor VIII and von Willebrand factor (VWF). A patient’s family history may be helpful, as most types of VWD are autosomal dominant, though two subtypes are recessive. Diagnostic evaluation of VWD VWF is the chaperone protein for factor VIII in the intrinsic pathway, which is measured by the PTT. In more severe forms of VWD, the PTT is prolonged because of factor VIII. VWF is measured separately because it is not reflected in the PT or PTT. The recommendation is to measure VWF antigen and employ a functional assay to see how well VWF binds platelets. The recommendation in the new guidelines is to use the GPIbM assay rather than the ristocetin cofactor assay. Many labs in the United States are still using the ristocetin cofactor assay. However, in Canada, Europe, and other parts of the world, many labs have moved to a newer assay that is automated. It has a much lower coefficient of variation and fewer issues with measurement of VWF in Black populations, which is a major issue with the cofactor assay. Types of VWD Type 1 VWD is characterized by a decreased amount of VWF. Type 1 patients have low VWF antigen and low platelet-dependent VWF function to a similar degree, with low or normal factor VIII. Type 2 VWD is characterized by aberrant VWF. The functional assay is a lot lower than VWF antigen. The platelet-dependent function to VWF antigen ratio cutoff is 0.7. Further testing is warranted to determine subtypes (2A, 2B, 2N, or 2M), including VWF multimers. Genetic testing can be helpful to further delineate subtypes. Type 3 VWD is characterized by the absence of VWF. The patient will have a VWF antigen level of 0, platelet-dependent VWF function of 0, and a reduced factor VIII level (usually less than 10%). Pregnant patients with VWD There is a protective adaptation in pregnancy, in which factors normalize in the third trimester, which works to prevent hemorrhage at delivery. This protective effect is because of the hormonal changes of pregnancy, and it is seen in patients with milder forms of VWD. WVF levels peak within 8-24 hours after delivery and then slowly return to baseline. There is a risk of delayed postpartum hemorrhage once VWF levels return to baseline, which tends to happen 7-14 days postpartum. Procedural planning: Desmopressin challenge test Desmopressin causes the release of VWF from the Weibel-Palade bodies of the endothelium, and it can be used as prophylaxis or treatment of bleeding in type 1 VWD. The desmopressin challenge test is used to check how the patient responds to desmopressin when well, to predict the patient’s response after an anticipated procedure. The test involves measuring VWF levels before desmopressin is given and at 1 hour, 2 hours, and 4 hours after desmopressin administration. The idea is to measure the magnitude of increase in VWF levels and observe how sustained that increase is to predict the patient’s response to desmopressin after future procedures. There is a subset of patients with type 1 VWD who have increased clearance of VWF that causes their decreased VWF levels. They may not have a sustained plateau in the VWF level after desmopressin, which emphasizes why testing as far as 4 hours after desmopressin administration is important. The dose of desmopressin given in this test is typically 0.3-0.4 mcg/kg. Recommendations for preprocedure prophylaxis for type 1 VWD Minor procedures (e.g., wisdom tooth extraction) The patient should receive an antifibrinolytic agent, such as tranexamic acid or aminocaproic acid, 2 hours before the procedure, followed by desmopressin 30-60 minutes prior to the procedure. After the procedure, the patient should continue to receive the antifibrinolytic agent for 3-4 days. Major procedures/surgeries (e.g., gallbladder removal) The guidelines do not recommend desmopressin for major procedures because patients need to be fluid-restricted for approximately 24 hours after administration because of the risk of hyponatremia. Desmopressin is a synthetic analog of vasopressin, which results in the accumulation of free water similarly to vasopressin. The guidelines do recommend giving VWF-containing concentrate to increase VWF and factor VIII to greater than 50% from baseline for at least 3 days. VWF concentrates can be given every 12 hours or as continuous intravenous infusions. Tranexamic acid should be given as an adjuvant both prior to the procedure and in the days following. Cryoprecipitate is not recommended because it can’t be virally inactivated.  Preprocedure prophylaxis in type 2 or 3 VWD Desmopressin does not work for most patients with type 2 or 3 VWD. So even for minor procedures, these patients will need to receive VWF concentrate coupled with antifibrinolytics. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Henry has no relevant disclosures. Dr. James disclosed relationships with Baxter/Baxalta/Shire, CSL Behring, Bayer, and Octapharma. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Brian Holoyda, MD, MPH, MBA, conducts a Masterclass on the history of psychedelic research and how the renaissance of this drug class could affect psychiatric patients. Dr. Holoyda, a forensic psychiatrist, practices in the San Francisco Bay Area. He also provides psychiatric consultations across the country. Dr. Holoyda has no disclosures. Take-home points The effects of psychedelics are dose dependent and difficult to predict. The impact of psychedelic treatment on violent behaviors was studied since the 1960s with varying results. More recent studies suggest that psychedelic use (excluding phencyclidine, or PCP) is associated with less violent crime. Dr. Holoyda recommends that, before psychiatrists treat patients with psychedelic-assisted psychotherapy, patients should be screened for history of violence or aggression while using psychedelics (and in general) and a history of serious mental illness. Patients require informed consent about the risk of violence and interventions used to control aggressive behaviors. Summary In 1960, the Harvard Psilocybin Project included a study in the Concord (Mass.) Prison in which researchers hypothesized that using psychedelic-assisted psychotherapy in prisoners would reduce risk of violent recidivism. The original authors, including Timothy Leary, PhD, published varying results of the study – including that psychedelic use reduced recidivism. However, some argue the overly positive results from the first analysis were attributable to a halo effect. A recent reanalysis showed that the base rate for recidivism in the intervention group was 34%, and not significantly different from that of the control group. Psychiatrists have continued to use psychedelic-assisted therapy for patients with psychopathology and treatment-resistant sexual offenders to investigate whether the transcendent experiences can change their personalities, including the development of insight and empathy. Dr. Holoyda published a review of all published cases in medical literature discussing psychedelic use and violent behavior. Most of the cases were published in the 1960s-1970s, when psychedelics were viewed negatively as a product of the counterculture era. More recent observational studies identified that psychedelics use is associated with a greater likelihood of carrying a firearm as well as intimate partner violence, but these newer studies are fraught, because PCP is sometimes classified as a psychedelic. Other epidemiological studies have identified reductions in violent behaviors associated with psychedelics use, compared with other illicit substances. Those reductions in violent behaviors include a lower probability of supervision failure, and a lower risk of intimate partner violence and drug distribution. Peter S. Hendricks, PhD, and associates analyzed data from 225 million individuals who took the National Survey on Drug Use and Health from 2002 to 2014 with a focus on psychedelics use, excluding PCP. They found that a lifetime history of psychedelic use decreased the odds of theft, assault, and arrest for property and violent crime. Studies such as this suggest that individuals who favor psychedelics may be less prone to violent crime rather than a direct effect of psychedelics on decreasing violent crime. As psychedelics enter the clinical sphere, clinicians must keep in mind that experiences on these agents are unpredictable. In a study of unmonitored psychedelic use, individuals report putting themselves or others at risk. Others reported behaving aggressively or violently, and others sought help at a hospital. Before using psychedelics in a therapeutic environment, clinicians should assess patients’ past use and experience on psychedelics. They also should screen for history of “bad trips,” leading to aggression, agitation, paranoia, and risky behaviors. In clinical trials with psychedelics, individuals with history of bipolar and psychotic disorders have been excluded to reduce the risk of triggering an episode. For medicolegal protection, psychiatrists should engage in a thorough informed consent process before using psychedelic-assisted therapy. References Holoyda B. Psychiatric Serv. 2020;71(12): 1297-99. Holoyda B. J Am Acad Psychiatry Law. 2020 Mar;48(1):87-97. Hendricks PS et al. J Psychopharmacol. 2017 Oct 17. doi: 10.1177/0269881117735685. Carbonaro TM et al.  J Psychopharmacol. 2016;30(12):1268-78. Metzner R. Reflections on the Concord prison project and the follow-up study. Bulletin of the Multidisciplinary Association for Psychedelic Studies/MAPS. Winter 1999/2000. 9(4). Arendsen-Hein GW. LSD in the treatment of criminal psychopaths, in "Hallucinogenic Drugs and Their Psychotherapeutic Use." (London: H. K. Lewis & Co, 1963). Leary T. Psyched Rev. 1969; 10:20-44. Leary T and Metzner R. Brit J Soc Psychiatry. 1968;2:27-51. Leary T et al.  Psychother. 1965;2:61-72. Doblin R. J Psychoactive Drugs. 1998; 30:419-26. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

We continue our review of drugs recently approved by the Food and Drug Administration (FDA) in the hematology/oncology space. In part 1 of our review, David M. Mintzer, MD, of Pennsylvania Hospital, highlighted 11 therapies, including newly-approved treatments and new indications for older drugs. Part 1 was published Feb. 18 (https://bit.ly/38JR782). Now, in part 2, Dr. Mintzer tells host David H. Henry, MD, about another 11 therapies recently approved by the FDA, including monoclonal antibodies, kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and more. Margetuximab-cmkb (Margenza) In Dec. 2020, margetuximab-cmkb was approved for use in combination with chemotherapy to treat adults with metastatic, HER2-positive breast cancer who had received at least two prior anti-HER2 regimens, including at least one for metastatic disease. https://bit.ly/38JAiKg Tafasitamab-cxix (Monjuvi) In July 2020, tafasitamab-cxix received accelerated approval for use in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant. https://bit.ly/3vtiHQF Lurbinectedin (Zepzelca) In June 2020, lurbinectedin received accelerated approval to treat adults with metastatic small-cell lung cancer with disease progression on or after platinum-based chemotherapy. https://bit.ly/30KcnpB Belantamab mafodotin-blmf (Blenrep) In Aug. 2020, belantamab mafodotin-blmf received accelerated approval to treat adults with relapsed or refractory multiple myeloma who had received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. https://bit.ly/3lkPLWd Umbralisib (Ukoniq) In Feb. 2021, the FDA granted umbralisib accelerated approval to treat adults with relapsed or refractory marginal zone lymphoma who had received at least one prior anti-CD20-based regimen and adults with relapsed or refractory follicular lymphoma who had received at least three prior lines of systemic therapy. https://bit.ly/3bQqtMM Azacitidine tablets (Onureg) In Sept. 2020, the FDA approved azacitidine tablets for continued treatment of patients with acute myeloid leukemia who had achieved a first complete remission or complete remission with incomplete blood count recovery after intensive induction chemotherapy and who are not able to complete intensive curative therapy. https://bit.ly/38KFT2Z Decitabine and cedazuridine tablets (Inqovi) In July 2020, the FDA approved an oral combination of decitabine and cedazuridine to treat adults with myelodysplastic syndromes (MDS). This includes previously treated and untreated, de novo and secondary MDS (including refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia), as well as intermediate-1, intermediate-2, and high-risk MDS. https://bit.ly/3lmqlI4 Tepotinib (Tepmetko) In Feb. 2021, the FDA granted accelerated approval to tepotinib for adults with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. https://bit.ly/3lmqBXy Pralsetinib (Gavreto) In Sept. 2020, pralsetinib received accelerated approval to treat adults with metastatic RET fusion-positive NSCLC. https://bit.ly/3vrS26I In Dec. 2020, the FDA granted full approval to pralsetinib to treat adult and pediatric patients ages 12 and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or those with RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine. https://bit.ly/3eCVXrs Brexucabtagene autoleucel (Tecartus) In July 2020, the FDA granted accelerated approval to brexucabtagene autoleucel, a CD19-directed CAR T-cell therapy, for the treatment of adults with relapsed or refractory mantle cell lymphoma. https://bit.ly/3tBtqH9 Lisocabtagene maraleucel (Breyanzi) In Feb. 2021, another CD19-directed CAR T-cell therapy, lisocabtagene maraleucel, was approved to treat adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The approval encompasses DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. https://bit.ly/3lljHBx Disclosures Dr. Mintzer and Dr. Henry have no relevant disclosures. * * * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Treatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) have advanced in recent years, with more new developments on the horizon. James Gerson, MD, of the University of Pennsylvania, Philadelphia, reviewed some of these advances and future directions while describing how he would treat three patients. Host David H. Henry, MD, posed the following cases for consideration. Case 1 In a 75-year-old male with no comorbid illness, routine blood work revealed a WBC count of 15,000/mcL. The manual differential showed mature lymphocytes and smudge cells. The patient has no constitutional symptoms, but there is suspicion of CLL. What to do? An incidental finding of elevated WBC is the most common presentation for CLL, Dr. Gerson noted. Flow cytometry is how most diagnoses are made. If the patient’s blood sample is CD5+ and CD20+, in the vast majority of cases, the patient has CLL. The main alternative diagnosis is MCL, so Dr. Gerson recommends checking for cyclin-D1 overexpression and translocation (11;14), which would be present in MCL. Dr. Gerson also recommends fluorescence in situ hybridization (FISH), cytogenetics, and next-generation sequencing to assist with prognostication. When the exam is normal and the patient is asymptomatic, no imaging is required. For this patient, treatment should be deferred until disease progression. Case 2 A 75-year-old, fit male has a WBC of 25,000/mcL, noted after the patient reported not feeling well, having a distended abdomen, night sweats, and weight loss. Blood work shows a hemoglobin level of 10.5 g/dL and a platelet count of 130 x 103/mcL. What to do? Because this patient is symptomatic, treatment is indicated, Dr. Gerson said. However, because of the pandemic, Dr. Gerson would likely delay therapy, perhaps until after COVID-19 vaccination. To assess risk, Dr. Gerson would perform immunohistochemistry, FISH, and next-generation sequencing in this patient. Patients with 17p deletion have high-risk disease, those with TP53 missense or nonsense mutations have even higher-risk disease, and patients with both a deletion and a mutation are “at excessively high risk,” Dr. Gerson said. He favors giving a BTK inhibitor to patients with TP53 mutation/17p deletion because of results from the CLL14 trial (N Engl J Med 2019; 380:2225-36. https://bit.ly/38pVHbf). However, because of the “small signal” in the trial, Dr. Gerson said plenty of his colleagues use a BTK inhibitor interchangeably with a BCL2 inhibitor and anti-CD20 therapy (e.g., venetoclax and obinutuzumab). Dr. Gerson said ibrutinib and acalabrutinib have similar efficacy, according to unpublished results of the ELEVATE-RR trial (https://bit.ly/38onIjy). Both drugs inhibit platelets, and there appears to be a higher risk of atrial fibrillation with ibrutinib. Case 3 A 75-year-old, fit male has an elevated WBC, noted after complaints of bone pain, weight loss, night sweats, and enlarged lymph nodes. There is suspicion of MCL. What to do? MCL is a complicated disease and “incredibly” heterogeneous in clinical and pathological behavior, Dr. Gerson noted. The classic finding in MCL is cyclin-D1 overexpression caused by (11;14) translocation, but there are atypical translocations as well. The approach to first-line treatment of MCL varies and may include cytarabine-based induction, bendamustine plus rituximab, or rituximab alone. Brexucabtagene autoleucel, a chimeric antigen receptor T-cell therapy, is changing the landscape of treatment for relapsed/refractory MCL, Dr. Gerson said, as this treatment may offer a cure. Investigational therapies for MCL include the BTK inhibitor pirtobrutinib (LOXO-305) and hematopoietic stem cell transplant. Pirtobrutinib is under investigation in patients with MCL, CLL, and other indolent lymphomas that have progressed on or are intolerant to first-line therapy (Lancet. 2021 Mar 6;397[10277]:892-901. https://bit.ly/3rvRv1h). Show notes written by Ronak Mistry, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Gerson disclosed relationships with Loxo Oncology, Genentech, Pharmacyclics, and TG Therapeutics. Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Pete Simi, PhD, joins host Lorenzo Norris, MD, to discuss some of the factors that lead people to join hate groups, and strategies that have enabled some to leave the life of extremism behind. Dr. Simi, associate professor of sociology at Chapman University in Orange, Calif., has studied extremist groups and violence for more than 20 years. His research has received external funding from the National Institute of Justice, the Department of Homeland Security, the Department of Defense, the National Science Foundation, and the Harry F. Guggenheim Foundation. Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. Dr. Norris has no disclosures. Take-home points Dr. Simi discusses how many of the White supremacists he studied live mundane, ordinary lives organized around extremist, violent beliefs. These individuals may be socialized in early life through exposure to beliefs consistent with White supremacy, such as racist ideas, slurs, and jokes, but they are not usually raised within a White supremacist family. The biggest challenge of leaving White supremacy is finding a new overarching identity, which ultimately requires redefining one’s emotional habits when it comes to engaging with society. White supremacist programming not only includes hateful beliefs but an emotional orientation that influences how an individual interprets the world around them. White supremacist violence and terrorism have long been a U.S. problem, and Dr. Simi said his awareness of the problem grew after the Oklahoma City bombing in 1995. Dr. Simi hopes that, through research and initiatives, the United States will address the root causes of White supremacist beliefs rather than focus on specific groups. Summary Dr. Simi first started studying White supremacists by evaluating their engagement on early Internet forums. Eventually, he made contact with a group that allowed him to observe their daily lives, including staying in their homes and attending collective events, such as music festivals. More recently, he has been evaluating and researching individuals who leave the White supremacist movement. As with many individuals who find solace in extremist groups, the childhood and adolescence of those who become White supremacists usually contain adverse childhood experiences and instability, such as physical and emotional abuse, and substance use in the home. These events cultivate vulnerability to White supremacy, because these adolescents and young adults are searching for a stabilizing force. In the Internet age, it’s much easier for vulnerable individuals to have chance encounters with extremist groups and beliefs, and even brief exposures are an opportunity for some to be recruited into White supremacist groups. A selling point of White supremacy is the sense of “fellowship” and “family,” which is attractive for individuals who feel disillusioned and isolated from society at large. In Dr. Simi’s research, half of his sample participants of White supremacists reported mental health diagnoses and similarly high rates of suicidal ideation. Mental illness is not an excuse for the behaviors and beliefs, but an example of another vulnerability that makes these individuals susceptible to strong support groups that often hold extremist beliefs. References Simi P et al. Am Sociol Rev. 2017 Aug 29. doi: 10.1177/00031224177282719. Bubolz BF and Simi P. Am Behav Sci. 2019. doi: 10.1177/0002764219831746. Simi P et al. J Res Crime Delinquency. 2016. doi: 10.1177/002242781567312. Windisch S et al. Terrorism Polit Violence. 2020. doi: 10.1080/09546553.2020.1767604. Ask a researcher: Pete Simi. What domestic groups pose the largest threats? University of Nebraska, Omaha. 2021 Jan 14. National Counterterrorism Innovation, Technology, and Education Center. A U.S. Department of Homeland Security Center of Excellence. McDonald-Gibson C. ‘Right now, people are pretty fragile.’ How coronavirus creates the perfect breeding ground for online extremism. Time. 2020 Mar 26. Garcia-Navarro L. Masculinity and U.S. extremism: What makes young men vulnerable to toxic ideologies. NPR. 2019 Jan 27. Life After Hate. Larry King Now. 2019 Jan 23. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

When should cancer patients receive a COVID-19 vaccine? The National Comprehensive Cancer Network (NCCN) has issued recommendations to provide guidance on the topic. Guideline author Steven Pergam, MD, of Fred Hutchinson Cancer Research Center, Seattle, explains NCCN’s recommendations to host David H. Henry, MD, in this episode. Prioritization Prioritization for COVID-19 vaccination should be given to cancer patients currently receiving chemotherapy, those who just finished active treatment, or those about to receive treatment. Additional factors that should be taken into consideration include age, comorbidities, and sociodemographic characteristics. Transplant and cellular therapy Patients who undergo allogeneic or autologous transplant or those who receive cellular therapy should be vaccinated at least 3 months after this treatment. This recommendation is based on best practices used for other vaccines, as there are insufficient data on COVID-19 vaccination in these patients, Dr. Pergam noted. Hematologic malignancies For patients with hematologic malignancies receiving intensive cytotoxic chemotherapy, vaccination should be delayed until absolute neutrophil count recovery. Patients with marrow failure from disease, those receiving therapy expected to have limited or no recovery, and those on long-term maintenance therapy should get vaccinated when a vaccine is available to them. Antibody response There are no current data to support checking antibodies prior to vaccination, as one will lose antibodies over time, Dr. Pergam noted. Likewise, there are no data to support testing for antibodies after vaccination. Solid tumor malignancies Patients with solid tumor malignancies who are receiving cytotoxic chemotherapy, targeted therapy, radiation, or checkpoint inhibitors or other immunotherapies should be vaccinated when a vaccine is available to them. For patients undergoing surgery, there should be adequate time between receiving a vaccine and the surgical date, as side effects from the vaccine, such as fever, can delay surgery. These guidelines are available for download from the NCCN website: https://www.nccn.org/covid-19/. Show notes written by Malika Gill, MD, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Pergam and Dr. Henry have no relevant disclosures. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Frank Chen, MD, joins host Lorenzo Norris, MD, to discuss the impact of the COVID-19 pandemic on patients with schizophrenia. Dr. Chen is the chief medical director for Houston Behavioral Healthcare Hospital and Houston Adult Psychiatry. He is a speaker for Alkermes and Otsuka. Dr. Chen has served on advisory boards for Alkermes, Intracellular Therapies, Otsuka, and Teva Pharmaceuticals. Dr. Norris is associate dean of student affairs and administration at George Washington University. He has no disclosures. Take-home points Schizophrenia is associated with an increased risk of death from COVID-19, even when controlling for other medical comorbidities. Individuals with schizophrenia have many biological and situational risk factors for COVID-19, including an elevated risk of metabolic syndrome from antipsychotic medications, higher rates of nicotine addiction, a greater likelihood of living in a group setting, limited access to medical care, and the underlying inflammatory state of schizophrenia. Summary An article published in JAMA Psychiatry in January 2021 evaluated a large cohort of patients in a New York health system and identified schizophrenia as the second most highly associated risk factor for 45-day mortality from COVID-19, after the risk factor of advanced age. The study controlled for other medical comorbidities to avoid confounding the results. However, it is essential to remember that individuals with schizophrenia have environmental and biological factors that increase their risk of infection and complications from COVID-19, such as metabolic syndrome, cigarette smoking, limited access to health care, and living in a group or institutional setting. Dr. Chen points out that many patients with schizophrenia already have skills to adapt to the stresses of the pandemic. For example, individuals with schizophrenia might already be accustomed to living with a certain level of fear and uncertainty inherent to their thought disorder. He also comments that negative symptoms make social distancing easier for individuals with schizophrenia than for other people. Dr. Chen notes that telepsychiatry has been a boon to treating individuals with schizophrenia, because using this tool is almost like making a “home visit.” Telemedicine removes the barriers to care, such as transport and resistance to coming to the office. Adaptation to telepsychiatry has varied among different patient populations. Dr. Chen says some of his “higher functioning” patients with more controlled and stable lives did not want to see their clinician via video. They preferred the “secure” and more private setting of an office. Ultimately, psychological flexibility and ability to adapt influence the amount of stress people experience during crisis. References Nemani K et al. JAMA Psychiatry. 2021 Jan 27. doi: 10.1001/jamapsychiatry. 2020.4442. Mazereel V et al. Lancet. 2021 Feb 3. doi: 10.1016/S2215-0366(2)30564-2. Muruganandam P et al. Psychiatry Res. 2020 Jun 29. doi: 101016/j.psychres.2020.113265. Kozloff N et al. Schizophr Bull. 2020 Jul;46(4):752-7. Smith BM et al. J Contextual Behav Sci. 2020 Oct;18:162-74. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Ifeyinwa (Ify) Osunkwo, MD, MPH, joins us to talk about her approach to pain management in patients suffering from sickle cell crisis as well as the cognitive and behavioral effects of long-term opioid use in these patients. She and our host David H. Henry, MD, cover these topics and more in this episode. Dr. Osunkwo is a professor of medicine at Atrium Health and the director of the Sickle Cell Enterprise at the Levine Cancer Institute, part of Atrium Health, in Charlotte, N.C. Over the course of a decade, the life expectancy of patients with sickle cell disease has increased. Today 99% of children with sickle cell disease will live to become adults. When treating patients with sickle cell pain it is important to consider their disease trajectory, and to weigh the pros and cons for initiation of opioid therapy. Management of sickle cell disease in the acute setting: In children, therapy usually includes use of intravenous fluid and intravenous opioids, then an eventual transition to oral opioids and NSAIDS. In adolescents, exposure to a prolonged course of high-dose opioids actually has been shown to exacerbate their pain. PCA (patient-controlled analgesia) versus “PRN” or as-needed medications removes the dependency on the external environment to receive pain medications and lessens the degree of psychological stress in these patients. Use of intravenous ketamine as an adjuvant to opioids in patients with an acute exacerbation has been shown to improve outcomes in patients (i.e., better pain control, decreased hospital stay, and management of anxiety and stress of a pain crisis.) In the acute pain setting, it is important to go through all differentials to get to where you are treating the right cause of pain. Following hospitalization, these patients often present back to the hospital in subacute opioid withdrawal. The key here is to engage patients in long term treatment plans. For opioid-induced itching, it has been shown that in patients who receive intravenous Benadryl have worse outcomes than in patients that receive oral Benadryl. Long-term side effects of chronic opioid therapy use: Psychological and behavioral side effects including insomnia, reduced libido, tolerance, oppositional behavior, poor memory, psychosis, paranoia, increased depression/anxiety and confusion. The opioid risk score is a helpful screening test that looks at the risk of adverse opioid outcomes. Specifically, family history of substance abuse, personal history of substance abuse, history of person abuse or psychological diagnosis results in a higher score which correlates with a higher risk of negative outcomes. Use of suboxone has proved to be very beneficial in patients on chronic opioid therapy in preventing frequent hospitalizations. Show notes written by Alesha Levenson, MD, a resident with Penn Medicine, Philadelphia. Disclosures Dr. Mintzer and Dr. Henry have no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

John Koo, MD, and Scott A. Norton, MD, MPH, join host Lorenzo Norris, MD, for this special edition of the Psychcast. This is a crossover episode with our sister podcast, Dermatology Weekly. Dr. Koo is a psychiatrist and a dermatologist at the University of California, San Francisco. He has no disclosures. Dr. Norton is a dermatologist with the Uniformed Services University of the Health Sciences in Bethesda, Md., and with George Washington University, Washington. He has no disclosures. They are featured in an article on this topic online at MDedge.com/Psychiatry. Dr. Norris is associate dean of student affairs and administration at George Washington University. He has no disclosures. Take-home points Delusional infestation or delusions of infestation, also known as delusional parasitosis, is a fixed false belief that one has an infestation of animate or inanimate pathogens, despite strong evidence against infestation. Common precipitants of delusional infestation include previous exposure to external or internal parasites, stress, and travel. The condition is more common among highly functional older women. A recent study estimated the prevalence of delusional infestation as 1.9/100,000, though the condition is an area of limited study. Delusional infestation is poorly recognized by physicians, therapists, and families, which leads patients to search for an external cause of the symptoms and contributes to distress for patients and their loved ones. Patients with delusional parasitosis often lack insight into their disease, and it can be difficult to persuade them to take the recommended treatment of antipsychotics. Low-dose pimozide, a first-generation antipsychotic, is the most common treatment for delusional infestation, particularly because it does not have Food and Drug Administration approval as a treatment for psychosis. Therefore, patients are less biased against taking this medication. Summary Delusions of infestation are a monosymptomatic hypochondriacal psychosis in which the only delusion present is one of infestation, and patients do not have other symptoms of psychotic spectrum illness. Secondary delusions of infestation may occur in individuals who use drugs, such as methamphetamine or cocaine, or who have a primary psychotic disorder, such as schizophrenia. Delusions of infestation is related to Morgellons disease, which is defined as a skin condition characterized by the presence of “threads” or filaments that patients believe are embedded in their skin and might be accompanied by stinging and itching sensations. Patients with delusions of infestation usually present to a primary care physician or ED with symptoms of abnormal sensations of their skin, including crawling sensations. In addition, patients usually bring personal proof of their condition, such as a small bag of “specimens,” including pieces of lint, threads, or scabs. Some patients also bring in journals detailing the timing and associated factors of their symptoms. Dr. Norton advises that physicians treating the patients with delusions of infestation should mentally prepare themselves against initial bias and set aside time for longer visits or several follow-up visits. Dr. Norton starts with the premise that the patient has an actual infestation or other underlying cause of their pruritus and performs a thorough, full-body exam for dermatologic conditions, and examines the materials patients bring with them using a double-headed microscope – so that he and the patient can look at the specimens together. Dr. Koo often tells patients that they have Morgellons disease because it does not include the stigmatizing term of “delusional.” He reframes Morgellons as an infestation that cannot be cured by internal or external antiparasitic medications. He then pivots away from etiology to validation of their emotions and eventually to treatment. Dr. Koo usually often starts treatment with pimozide because it is an antipsychotic with FDA approval for Tourette syndrome – not schizophrenia. This perceived absence of a connection of the medication to psychiatric illness allows patients to be more open to taking the medication. For primary delusional infestation, Dr. Koo starts with pimozide. The dose, which is daily and taken orally, starts low at 0.5 mg and goes up by 0.5 mg every 2-4 weeks. The aim is to get up to 3 mg per day. Low doses of pimozide and other antipsychotics lead to decreased sensation of itching and formication. Dr. Koo refers to his treatment plan as a “trapezoid-like dosage strategy.” Once he gets the patient to 3 mg, he continues the medication until all the symptoms disappear and then continues the medication for an additional 3 months. Dr. Koo then slowly tapers the dosage over an additional few months. The keys to successful treatment include communicating with patients and working collaboratively with them. This approach builds trust and rapport. References Brown GE et al. J Clin Exp Dermatol Res. 2014;5:6. doi: 10.4172/2155-9554.1000241. Kohorst JJ et al. JAMA Dermatol. 2018 May 1;154(5):615-7. Lepping P et al. J Am Acad Dermatol. 2017 Oct;77(4):778-9. Middelveen MJ et al. Clin Cosmet Investig Dermatol. 2018;11:71-90. Lepping P et al. Acta Derm Venereol. 2020 Sep 16. doi: 10.2340/00015555-3625. Freudenmann RW et al. Br J Dermatol. 2012 Aug;167(2):247-51. Wolf RC et al. Neuropsychobiology. 2020;79:335-44. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

In this episode, we review drugs recently approved by the Food and Drug Administration in the hematology/oncology space. David M. Mintzer, MD, of Pennsylvania Hospital, joins host David H. Henry, MD, to highlight some first-time approvals and new indications for older drugs. Approvals in 2020 Pembrolizumab (Keytruda) was approved for a range of new indications last year, including: First-line treatment of patients with unresectable or metastatic microsatellite instability–high or mismatch repair deficient colorectal cancer. https://bit.ly/2OKw8uF. Treatment of adult and pediatric patients who have tumor mutational burden–high (≥10 mutations/megabase) solid tumors that progressed after prior treatment and who have no satisfactory alternative treatment options. https://bit.ly/2NCddkX. For use in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 (combined positive score ≥10) as determined by an FDA-approved test. https://bit.ly/2ZobcMc. To treat patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation. https://bit.ly/3ashYGV. Avelumab (Bavencio) was approved for maintenance therapy in patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. https://bit.ly/3ar8XOs. Nivolumab (Opdivo) was approved for: Patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy. https://bit.ly/3ar4bjX. Use in combination with ipilimumab as first-line treatment in adults with unresectable malignant pleural mesothelioma. https://bit.ly/2NbQ60V. Atezolizumab (Tecentriq) was approved in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. https://bit.ly/2NzkodG. Osimertinib (Tagrisso) was approved for adjuvant therapy after tumor resection in patients with non–small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. https://bit.ly/2NC0aQs. Selinexor (Xpovio) was approved for: Use in combination with bortezomib and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior therapy. https://bit.ly/3s1u1kp. Adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including disease arising from follicular lymphoma, after at least two lines of systemic therapy. https://bit.ly/2M172GW. The FDA also approved a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) for subcutaneous injection for:  Use in combination with chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. Use in combination with chemotherapy as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence. Use in combination with docetaxel to treat patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. https://bit.ly/2LXA4XX. Relugolix (Orgovyx) was the first oral gonadotropin-releasing hormone receptor antagonist approved by the FDA for adults with advanced prostate cancer. https://bit.ly/3qyJisQ. Approvals in 2021 Cemiplimab-rwlc (Libtayo) was approved for patients with locally advanced or metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. https://bit.ly/3ppkW31. Daratumumab plus hyaluronidase (Darzalex Faspro) was approved in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed light chain amyloidosis. https://bit.ly/3bbaF5I. Approval in 2019 In late 2019, the FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. https://bit.ly/3qw9tA4. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Mintzer and Dr. Henry have no relevant disclosures. * * * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

George T. Grossberg, MD, conducts a Masterclass examining emerging treatment options for Alzheimer’s disease that are tied to the new research on the microbiome. Dr. Grossberg is the Samuel W. Fordyce professor and director of geriatric psychiatry in the department of psychiatry and behavioral neuroscience at Saint Louis University. He disclosed that he is a consultant for Acadia, Alkahest, Avanir, Axovant, Axsome Therapeutics, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Novartis, Otsuka, Roche, and Takeda; receives research support from the National Institute on Aging, Janssen, and Genentech/Roche; performs safety monitoring for ANAVEX, EryDel, Intra-Cellular Therapies, Merck, and Newron; and serves on the data monitoring committee of ITI Therapeutics. Dr. Grossberg also serves on the speakers’ bureau of Acadia. Take-home points Dr. Grossberg discusses burgeoning research about treatment of Alzheimer’s disease (AD) by altering the microbiota using diet and medications. The microbiome refers to the entirety of microorganisms that live throughout the body. Microbiota are those organisms that live within the gut. Dysbiosis refers to a microbial imbalance, which has been linked to numerous disorders, including inflammatory diseases, psychiatric illness, obesity, diabetes, and more recently, AD. The gut-brain axis describes the impact of microbiota and GI tract health on the brain. Periodontal disease, as a marker of inflammation and as part of the microbiome, is linked to AD. Increasing research into the role of the microbiome, inflammation, and AD has revealed promising treatments. Sodium oligomannate, a drug approved for mild to moderate AD in China, has been shown to slow the progression of AD by remodeling the microbiota and suppressing the production of specific amino acids that promote neuroinflammation. Summary The microbiota has many purposes, including digestion, communication with the immune system, generation of signaling peptides, refining vitamins, and producing antioxidants. Many factors influence the microbiome, including diet, use of antibiotics, exposure to breast milk as an infant, stress, and old age. The gut microbiota can be altered by consuming “prebiotics,” which are food sources that influence the composition of the microbiota. These foods include fermented foods such as yogurt, kombucha, sauerkraut, and kimchi. The Mediterranean diet also has good sources of prebiotics. Birthing method (C-section versus vaginal birth) also influences the microbiota; a recent study shows that an infant’s microbiota after C-section can be altered by giving them an early fecal transplantation from the mother. As further proof of the link between periodontal disease and AD, a recent study identified the presence of Porphyromonas gingivalis, a bacteria that causes gum disease, in the brain in close proximity to the tau tangles of AD. Gingipain, the toxin secreted by this bacteria, is found in high concentrations in brains of individuals with AD. Dr. Grossberg reviewed his “recipe” for AD prevention and treatment: Recommend adequate activity in four spheres: Physical, mental, social, and spiritual. Treat and control all cardiovascular risk factors, including smoking, obesity, diabetes, hypertension, and hyperlipidemia. Recommend good oral hygiene based on the increasing research about the link of periodontal disease and AD. Recommend dietary changes, including a prebiotic or probiotic, and the Mediterranean diet. Dietary changes may also include supplements such as curcumin, B-complex multivitamin, and vitamin E. Control exposure to air pollution as possible. Use a combination pharmacotherapy of an N-methyl-D-aspartate antagonist and a cholinesterase inhibitor for individuals with AD. References Jones ML et al. Gut Microbes. 2014 Jul 1;5(4):446-57. Askarova S et al. Front Cell Infect Microbiol. 2020;10:104. Beydoun MA et al. J Alzheimers Dis. 2020;75(1):157-72. Wang X et al. Cell Res. 2019 Oct;29(10):787-803. Korpela K et al. Cell. 2020 Oct 15;183(2):324-34. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

The NCI-MATCH trial was designed to reveal mutations in underexplored cancer types, allowing researchers to match patients to appropriate targeted therapies. Study investigator Alice P. Chen, MD, from the National Cancer Institute, reviews the goals and results of NCI-MATCH with host David H. Henry, MD, in this episode. Trial details NCI-MATCH has more than 1,000 participating sites. The trial is open to patients with advanced cancers that have progressed on standard treatment or rare cancers for which there is no standard treatment. Investigators use next-generation sequencing to identify mutations in tumor biopsies taken before the start of therapy. Sequencing is performed at MD Anderson Cancer Center, Houston; Massachusetts General Hospital, Boston; MoCha at NCI’s Frederick (Md.) National Lab; Yale University, New Haven, Conn.; and commercial labs. Matching patients to treatment When a patient is found to have an actionable mutation, that patient is assigned to an investigational treatment, typically monotherapy. A patient cannot be assigned to a treatment that is already known to be effective against their cancer; for example, patients with BRAF-mutated melanoma were excluded. The NCI’s Cancer Therapy Evaluation Program sends the patient's targeted therapy to the participating site within 24 hours of notification. CT imaging is done prior to the start of treatment, and patients are monitored with repeat scans every two cycles. Results Data on 5,954 patients with refractory malignancies were recently reported (J Clin Oncol. 2020 Nov 20;38[33]:3883-94). About 38% of those patients had an actionable mutation, and about 18% were assigned to a targeted therapy. Reports have shown varying response rates to matched therapy, ranging from 2% to 38%, Dr. Chen said. Results from the trial's treatment arms can be found here: https://ecog-acrin.org/nci-match-eay131-findings. Dr. Chen noted that this trial was designed to match patients with single agents. Combination therapy has only been used in one arm of the study (J Clin Oncol. 2020 Aug 06. doi: 10.1200/JCO.20.00762). Future directions Nine treatment arms are still open, and one arm has yet to open. Conclusions are still pending the completion of the treatment arms. The next step for this research is expanding to include more combination therapies. There is also interest in comparing biopsies of tissue obtained at initial diagnosis and after treatment to further improve understanding of mutations. For more information on NCI-MATCH, visit: https://www.cancer.gov/about-cancer/treatment/clinical-trials/nci-supported/nci-match. https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCT02465060. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Chen and Dr. Henry have no conflicts of interest. *  *  * For more MDedge Podcasts, go to www.mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Rebecca W. Brendel, MD, JD, and Allen R. Dyer, MD, PhD, join guest host Carol A. Bernstein, MD, to discuss the ethical challenges that have been occurring during the COVID-19 pandemic. Dr. Brendel is director of law and ethics at the Center for Law, Brain, and Behavior at Massachusetts General Hospital, Boston. She also serves as director of the master of bioethics degree program at Harvard Medical School, Boston. Dr. Brendel has no disclosures. Dr. Dyer is professor of psychiatry and behavioral sciences at George Washington University, Washington. He also serves as vice chair for education at the school of medicine and health sciences. Dr. Dyer has no disclosures. Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore Medical Center/Albert Einstein College of Medicine, New York. She has no disclosures. Take-home points Medical ethics often deal with decisions between doctors and patients, but during the COVID-19 pandemic, the medical community has been forced to reckon with ethics on a population scale. Examples of ethical challenges include issues of scarcity, justice, transparency, and navigating distrust of the medical system. In the beginning of the pandemic, individuals such as Dr. Brendel and Dr. Dyer participated in ethical planning so that hospital systems would be prepared to deal with scarcity of resources that could result in some individuals going without lifesaving interventions. During times of scarcity, transparency and accountability are necessary, because the community will ask questions about the fairness and justice of specific outcomes. The philosophy of utilitarianism is a reason-based decision-making model that strives to maximize the greatest good for the greatest number, and it has been commonly used as a template for ethical discussions during the pandemic. Yet, utilitarianism calculus is complicated by questions of how to define “good” and the challenge of accurately predicting the outcomes. Summary In situations of urgency, demand, and scarcity, ethics usually turns to utilitarianism with the intention of maximizing the greatest good for the greatest number. Inevitably, people or populations are harmed. Especially in the beginning of the COVID-19 pandemic, American society grappled with the issue of scarcity and allocation of medical resources, ranging from personal protective equipment, ventilators, medical staff, ICU space, and the vaccine.   Now we must think about the ethical decisions influencing COVID-19 vaccination, including weighing the risks and benefits of who gets the vaccine and when – and how certain vaccine schedules forestall the spread in the population. For example, institutionalized individuals are at great risk of contracting COVID-19, yet society debates the “good” of vaccinating elderly in nursing homes versus incarcerated individuals. Question of defining good and grappling with the consequences are present throughout the entire vaccination algorithm. Communities contend with the question of who in their ranks are essential workers: Health care workers? Teachers? Restaurant staff? Factory workers? Justice and transparency are commonly discussed ethical principles, especially when we think about the algorithms created to allocate resources. Transparency is required to foster trust in the public health system, and actors within the system must demonstrate their accountability through being honest about the evidence behind policy decisions, following set parameters, and acknowledging historical reasons for distrust. The pandemic has pushed society to think about the ethics of community solidarity and reflect on governmental and individual responsibility of protecting the health and well-being of the community. As the pandemic ravaged the U.S. economy and further disadvantaged already vulnerable communities, we must use this opportunity to reexamine the ethics of how health care is distributed in the United States, and work toward a just and equitable system. References Ethics and COVID10: Resource allocation and priority-setting. 2020 World Health Organization. AMA Journal of Ethics. COVID-19 Ethics Resource Center. Emanuel EJ et al. N Engl J Med. 2020 May 21. doi: 10.1056/NEJMsb2005114. Dyer AR and Khin EK. Int Encycl Soc Behav Sci. 2015;63-70. The principles of medical ethics with annotations especially applicable to psychiatry, 2013 edition. American Psychiatric Association. American Psychiatric Association. Ethics.psychiatry.org.  *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com  

How do the various COVID-19 vaccines work, and when should patients be vaccinated? We tackle these topics and more in this episode. Our host David H. Henry, MD, is joined by Drew Weissman, MD, PhD, a professor at the University of Pennsylvania, Philadelphia. Dr. Weissman codeveloped the messenger RNA (mRNA) technology being used in the COVID-19 vaccines produced by Pfizer/BioNTech and Moderna. History of mRNA vaccines Testing of mRNA vaccines began in the 1990s. An initial problem with these vaccines was that the RNA was highly inflammatory. Dr. Weissman and his colleague, Katalin Karikó, PhD, discovered how to fix that problem in 2005. The pair found that placing modified nucleosides into mRNA made it noninflammatory and allowed for increased production of protein from the RNA – up to a 1,000-fold increase in mice. This technology is the basis of the Moderna and Pfizer/BioNTech COVID-19 vaccines. Immunology and vaccines To produce a good immune response, antigen must be present for a long time, though the optimal amount of time is unknown, Dr. Weissman said. The mRNA lipid nanoparticles (LNPs) used in the COVID-19 vaccines make protein for 10-14 days, resulting in a “great” immune response, according to Dr. Weissman. Most vaccines have an adjuvant, or something that stimulates the immune response by inducing TH1 or TH2 responses. The LNP used in the COVID-19 vaccines is an adjuvant that makes a specialized CD4 helper cell that drives antibody production, increases antibody affinity, and matures antibodies to make long-lived plasma cells to allow for long-lived antibody responses. This is the only adjuvant known that induces these type of helper T cells. COVID-19 vaccine reactions Adverse reactions to COVID-19 vaccination – flu-like symptoms, arm pain, etc. – are caused by the LNP, not the spike protein. Once the LNP is gone, usually within the first 24 hours, symptoms dissipate. The amount of spike protein produced decreases over 14 days. It’s unclear if patients should take NSAIDs to manage symptoms after COVID-19 vaccination, as this hasn’t been tested. However, with influenza vaccination, taking an NSAID will decrease the immune response. Variants and their impact on vaccination SARS-CoV-2 variants have been reported in Brazil, South Africa, California, and the United Kingdom. Dr. Weissman explained that there are two kinds of variation: when a virus learns how to better infect people and when the virus learns to avoid immune responses. Most SARS-CoV-2 variants are equally addressed by the vaccines, though we know vaccines have reduced efficacy against the South African variant, Dr. Weissman said. The good news is that coronavirus mutates very slowly, and it’s easy with mRNA vaccines to “plug in” a mutant and make a more effective vaccine, Dr. Weissman said. Vaccinating cancer patients: Treatment considerations For patients receiving chemotherapy: We don’t know the best time to administer COVID-19 vaccines to patients on chemotherapy, as this hasn’t been studied, Dr. Weissman said. When other vaccines were given to subjects receiving chemotherapy, those vaccines did not work as well. Chemotherapy knocks down myeloid cells around day 7, with recovery typically around day 28. Dr. Weissman said he would probably vaccinate at day 14 in the chemotherapy cycle, as the germinal centers where B cells are produced form about 2-7 days after receipt of the vaccine. For patients receiving checkpoint inhibitors: The optimal time for vaccination in patients receiving checkpoint inhibitors is unknown. However, the immune response to vaccination in patients on checkpoint inhibitors is expected to be similar to the general population or slightly enhanced. For patients receiving anti-CD20 antibodies: Anti-CD20 antibodies might blunt the B-cell response to vaccination. Rituximab, for example, depletes B cells in the circulation for months. In the absence of B cells, there won’t be a good antibody response. T-cell response is also stimulated by COVID-19 vaccines, but we don’t know how effective that response will be in protecting against infection, Dr. Weissman said. Vaccinating HIV patients Patients with well-controlled HIV (i.e., low viral load and CD4 counts >200) should generate a good immune response, Dr. Weissman said. Patients with poorly controlled HIV (i.e., high viral loads and low CD4 counts) are likely to have a poor immune response to vaccination, though it isn’t clear how poor the response will be. Should patients who recently had COVID-19 get vaccinated? Clinicians are waiting 90 days to vaccinate patients who have a positive COVID-19 test, Dr. Weissman said. In 95% of cases, SARS-CoV-2 infection conveys protective antibodies for at least 3 months. Patients with recent SARS-CoV-2 infection have more severe adverse reactions to vaccination (e.g., fever, arm pain, flu-like symptoms). It’s safe to wait until 2 weeks after recovery from infection before receiving the vaccine, and vaccination is expected to work well with a boosted immune response, Dr. Weissman said. Is there any role for checking antibody status after vaccination? Phase 3 trials of the Pfizer/BioNTech and Moderna vaccines showed that levels of neutralizing antibodies were higher in vaccinated patients than in those who had recently been infected; i.e., vaccines give a better immune response than infection. The durability of response to the vaccines is unknown, but studies are underway. The challenge for clinicians is that the antibody assays available are not directed at the spike protein, and they are not quantitative. Vaccine on the horizon The COVID-19 vaccine under development by Johnson & Johnson uses adenovirus. The spike protein is inserted into the genome of the adenovirus, and the virus is altered so it cannot replicate, thus preventing its spread. The live virus stimulates the cells to make a better immune response. This type of vaccine is potent and produces lower antigen levels than mRNA vaccines but with better T-cell responses, Dr. Weissman said. On Jan. 29, Johnson & Johnson released phase 3 data for this vaccine (https://bit.ly/3oNXX1k). The vaccine was reported to be 85% effective overall in preventing severe COVID-19. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Weissman disclosed royalties from Moderna and Pfizer/BioNTech. Dr. Henry has no disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Ruth S. Shim, MD, MPH, joins Carol A. Bernstein, MD, to discuss how to understand systemic racism within psychiatric institutions and the implications for patient care. Dr. Shim is the Luke & Grace Kim Professor in Cultural Psychiatry in the department of psychiatry and behavioral sciences at the University of California, Davis. She has no disclosures. Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore Medical Center/Albert Einstein College of Medicine, New York. She has no disclosures. Take-home points Dr. Shim discusses her editorial published by statnews about why she left the APA, and describes her frustration about what she sees as the APA’s failure to prioritize mental health inequity and structural racism within the organization. Dr. Shim describes systemic racism and oppression as generational traumas that must be recognized and processed if our professional organizations and country are to move forward with equity. Psychiatry plays a role in healing societal trauma, so psychiatrists need to understand and address the damage of structural racism in our own system. Summary After psychiatry training, Dr. Shim became faculty at Morehouse School of Medicine, one of the few historically Black medical schools. During her clinical work in Atlanta, Dr. Shim noted the difference in health outcomes of inpatients at Emory University Hospital, which treated majority White patients, compared with those of Grady Memorial Hospital, which treated majority Black patients. This observation propelled her research into health disparities, which continues to inform her academic work. Dr. Shim’s decision to leave the APA occurred during the presidential term of Altha J. Stewart, MD, who, even as the first African American president of the organization, was thwarted in her attempt to push the APA to focus attention and resources on addressing mental health disparities, inequity, and systemic racism within the organization and psychiatry, according to Dr. Shim. Dr. Shim observes that systemic racism occurs when the structures of an organization, not individuals, perpetuate the inequity. An example within the APA is the disconnect and power disparity between the group’s executive leadership structure and its elected officials. This disconnect and power disparity stymie progressive voices and interventions, Dr. Shim said. Addressing systemic racism within an organization is challenging because it may not be considered a problem by all members, and usually the leadership of an organization caters to its majority. As an example, Dr. Shim discussed the APA’s systematic attempt to reduce resources and cancel the Mental Health Services Conference (formerly Institute for Psychiatric Services, or IPS meeting), which focuses on health care delivery to the most vulnerable populations. As observed by Dr. Bernstein, the IPS meeting might have incurred financial losses, but investment in such a meeting demonstrated the APA’s concern for mental health equity. (The Mental Health Services Conference was not held in 2020 but is scheduled to be held virtually Oct. 7-8, 2021). References Shim RS and Vinson SY, eds. Social (In)Justice and Mental Health. Washington, D.C.: American Psychiatric Association Publishing, 2021. Shim RS. Structural racism is why I’m leaving organized psychiatry. Statnews.com. 2020 Jul 1. Marmot M et al.  Lancet. 2008 Nov 8;372(9650):1661-9. Okun T. White supremacy culture. Dismantlingracism.org. APA apologizes for its support of racism in psychiatry. psychiatry.org. 2021 Jan 18. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

The greatest barrier to clinical trial enrollment is patients not knowing an appropriate trial exists, according to a survey of gynecologic cancer survivors. The most common reason survey respondents gave for not enrolling in clinical trials was that their medical team didn't tell them about any trials. Annie Ellis and Mary (Dicey) Jackson Scroggins – who are both patient advocates and ovarian cancer survivors – conducted this survey and presented the results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer last year (https://bit.ly/3plI1Vg). Ms. Ellis discussed the survey results and other related research with host David H. Henry, MD, in this episode. Ms. Ellis and Ms. Scroggins distributed their 26-question survey online. The survey was completed by 189 survivors of gynecologic cancers. Most respondents (65.6%) had never participated in a clinical trial. Reasons for nonparticipation included: The medical team never discussed trial participation (50.4%) The patient didn’t qualify for a trial (14.4%) The trial location was too far away (7.2%) The desired trial wasn’t available (4.0%) Insurance didn’t cover trial participation (1.6%) The patient didn’t want to receive a placebo (11.2%), wasn’t interested in experimental therapies (3.2%), didn’t want to be randomized (2.4%), or didn’t trust the medical system (1.6%) Other reason (fill in the blank; 38.4%). Roughly a third of respondents (34.4%) had participated in a clinical trial. Most of these respondents (86.2%) learned about the trial from their doctor. All past trial participants said they would participate again (84.6%) or they were not sure about future participation (15.4%). Ms. Ellis also mentioned a recent review and meta-analysis, which showed that more than half of all cancer patients offered a clinical trial do participate (J Natl Cancer Inst. 2020 Oct 6. doi: 10.1093/jnci/djaa155. https://bit.ly/2Yg4dnP). Together, these finding suggests cancer patients may be willing to participate in trials but often don’t know that relevant trials exist. Ms. Ellis noted that her colleague, Ms. Scroggins, often says, “Patients can't go to the party if they don't get an invitation.” Disclosures Ms. Ellis, Ms. Scroggins, and Dr. Henry have no conflicts of interest. * * * For more MDedge Podcasts, go to www.mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

David H. Rosmarin, PhD, joins Lorenzo Norris, MD, to discuss how to think about the concept of denial and its role in the sociopolitical challenges of our society. Dr. Rosmarin is a clinical psychologist and director of the spirituality and mental health program at McLean Hospital in Belmont, Mass. He also is an assistant professor of psychiatry at Harvard Medical School, Boston. Dr. Rosmarin has no disclosures. Dr. Norris has no disclosures. Take-home points Denial is defined as a cognitive and emotional process by which a person avoids facing aspects of reality, especially when it is difficult to assimilate the details of reality into one’s current thinking. Arguably, denial is a coping or defense mechanism meant to address the tension that arises from trying to change an individual’s current way of thinking and understanding of reality. Another form of denial is choosing to focus only on one’s perception of reality and struggling to see the other side of an argument. We can see this form of denial play out in COVID-19 pandemic denial and in certain political narratives. Denial in its most potent form causes individuals to disconnect from any conversation around the salient topic, which can make denial even worse. Summary Denial can be adaptive in its role of protecting a person's psyche. When the midbrain and limbic system are activated, the frontal lobe needs time to process and integrate the information. For example, people will deny the presence of an event they regret or fear until they have enough emotional capacity to integrate new facts into their current model of reality. Yet, denial can be harmful when there are “side effects.” The classic example of pathologic denial is an individual who has experienced trauma, and through continued denial of its impact and poor integration of the event, starts to experience somatic symptoms. Dr. Rosmarin says the problem with denial is that people who are experiencing denial are often the last to recognize their need for treatment or an intervention. Dr. Rosmarin discusses how, with certain topics, we must value and preserve relationships over persuading certain social contacts, such as family and friends, to overcome their denial. Validating emotions and finding the validity in a person's beliefs and grievances can go a long way toward preserving relationships that are challenged by denial of certain facts. References Rosmarin DH et al.  Lancet Psychiatry. 2021 Feb;8(2):92-3. Hall C and Pick D.  Hist Workshop J. 2017 Oct;84(1):1-23. Miller BL. JAMA. 2020 Dec 8;324(22):2255-6. Rosmarin DH. Spirituality, Religion and Cognitive-Behavioral Therapy: A Guide for Clinicians. New York: Guilford Press, 2018. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

New studies have shed additional light on how convalescent plasma may affect patients with COVID-19, how blood type impacts bleeding risk, the effects of race on cancer-associated thrombosis, and iron deficiency in pregnancy. These studies were presented as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology. Alisa S. Wolberg, PhD, of the University of North Carolina at Chapel Hill, who cochaired the session, reviews these studies with host David H. Henry, MD, in this episode.   Abstract #572: Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause. https://bit.ly/2Mc0R2A. This study, which included 422 patients, indicated that blood group O is overrepresented in patients with bleeding of unknown cause. Blood group O was associated with a more severe bleeding phenotype, especially oral mucosal bleeding, independent of the levels of von Willebrand factor and factor VIII. Patients with blood group O had increased clot density, but blood group O didn’t influence thrombin generation or platelet function analysis. The researchers said these findings are important for better understanding the underlying mechanisms of bleeding in patients who have bleeding of unknown cause. Dr. Wolberg said this study reframed how people look at bleeding of unknown cause. Abstract #203: Racial/Ethnic Disparities in Cancer-Associated Thrombosis: A Population-Based Study. https://bit.ly/35Xi5HE. This study included more than 942,109 cancer patients. Results showed an independent association between race/ethnicity and the risk of cancer-associated thrombosis. Asians/Pacific Islanders had a significantly lower incidence of cancer-associated thrombosis, compared with non-Hispanic Whites. African Americans had a significantly higher incidence of cancer-associated thrombosis versus non-Hispanic Whites. Racial/ethnic differences were especially prominent when examining pulmonary embolism only. It’s hard to determine what causes these differences, Dr. Wolberg said. The differences could be explained by underlying biological traits, systemic racism, access to care, and/or the severity of underlying comorbidities, according to the researchers. Abstract #424: Suboptimal Iron Deficiency Screening in Pregnancy in a High Resource Setting. https://bit.ly/2XYedSA. The study included data on 47,590 pregnancies in 44,552 women from Ontario. About 40% of these patients (n = 25,880) had ferritin measurements taken during pregnancy. Iron deficiency was observed in 52.8% of evaluable pregnancies, and severe iron deficiency was seen in 23.8%. These findings suggest a ferritin test should be included as part of routine bloodwork at the first prenatal visit, the researchers said. They also noted that failing to evaluate iron stores in the second and/or third trimester misses the periods of highest iron-deficiency risk, when intravenous iron may be considered. The researchers said these gaps in care should be addressed by revising guidelines. Abstract #245: Efficacy of COVID-19 Pathogen-Inactivated Convalescent Plasma for Patients with Moderate-to-Severe Acute COVID-19: A Case-Matched Control Study. https://bit.ly/2XVlulU. For this study, researchers compared 15 cases and 30 controls, all of whom had COVID-19. Cases received two units of COVID-19 convalescent plasma (CCP) from different donors. CCP appeared to improve survival in hospitalized COVID patients, though the difference was not significant. The 28-day mortality rate was 6.7% among cases and 20.7% in controls (P = .233). The researchers also found that unselected CCPs have heterogeneous antivirus activity. Pathogen reduction treatment did not impact antivirus activity. ADAP, ACE2, RVPN, and COVAM could be used to define activity. A posttransfusion increase in activity could be detected in some, but not all, patients. The researchers said more definitive studies are needed. *Some of the data presented at the meeting differ from data included in the abstracts. Disclosures: Dr. Wolberg disclosed relationships with Bristol-Myers Squibb, GlaxoSmithKline, and Takeda. Dr. Henry has no financial disclosures relevant to this episode. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Guest host Eva Ritvo, MD, interviews Dorothy Otnow Lewis, MD, about her more than 40-year career in studying death row inmates as examined in the HBO documentary “Crazy, Not Insane.” Dr. Lewis is clinical professor of psychiatry at Yale University, New Haven, Conn. She has no disclosures. Dr. Ritvo is a psychiatrist in private practice in Miami Beach, Fla. She has no disclosures. Take-home points Dr. Lewis has an extensive archive of taped interviews with death row inmates that she has used to inform her work as an expert witness. While doing her child psychiatry training at the Yale Child Study Center and sitting in at the juvenile court, she began to see that some of the children had psychiatric and neurologic problems that had not been addressed. The parents of these children sometimes had psychotic or bipolar disorders. After seeing these themes, Dr. Lewis started a clinic at the court. Dr. Lewis and her team were able to study approximately 15 inmates in four states, including Texas and Florida, both of which had the greatest number of condemned juveniles. One key theme that emerged is that all of the inmates had been sentenced to death as juveniles. Eventually, the Supreme Court ended the death penalty for convicted killers who committed their crimes before age 18. Digging deeper and asking more questions of child and adolescent patients who commit violent acts can help clinicians identify environmental stressors that might underlie behavior that is aggressive and antisocial. In some cases, the psychiatric and neurologic impairments identified are treatable. Dr. Lewis would like to study whether identifying child abuse early might prevent future violence. References Yaeger CA, Lewis DO. Mental illness, neuropsychologic deficits, child abuse and violence. Child Adolesc Psychiatr Clin N Am. 2009;(4):793-813. Lewis DO. Ethical Implications of what we know about violence. Child Adolesc Psychiatr Clin N Am. 2000 Oct 9(4):833-91. Lewis DO et al. Ethics questions raised by the neuropsychiatric, neuropsychological, educational, developmental, and family characteristics of 18 juveniles awaiting execution in Texas. J Am Acad Psychiatry Law. 2004;32(4):408-29. Griffith EEH et al. Re: Ethics questions raised by characteristics of 18 juveniles awaiting execution in Texas.     J Am Acad Psychiatry Law. 2006;34(2):143-4. Lewis DO et al. Some evidence of race bias in the diagnosis and treatment of the juvenile offender. Am J Orthopsychiatry. 1979 Jan;49(1):53-61. Lewis DO. Guilty by Reason of Insanity: A Psychiatrist Explores the Minds of Killers. New York: Fawcett Columbine, 1998. Roper v. Simmons, 543 U.S. 551 (2005). Thompson v. Oklahoma, 487 U.S. 815 (1988) .   For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com  

Three studies revealed new findings on thrombosis in patients with cancer and/or COVID-19. These studies were presented at the 2020 annual meeting of the American Society of Hematology. One study suggested the Khorana score may be ineffective for predicting venous thromboembolism (VTE) in cancer patients. Another study revealed factors that can predict VTE in patients with cancer and COVID-19. And a third study indicated that antithrombotic agents don’t improve outcomes in patients with severe COVID-19.  Kristen M. Sanfilippo, MD, of Washington University, St. Louis, reviews these studies with host David H. Henry, MD, in this episode. Abstract 202: Performance of Khorana Score to Predict One-Year Risk of Venous Thromboembolism in Over Two Million Patients With Cancer. https://bit.ly/3oCHOfQ. The study included 2,112,260 patients with cancer. At 1 year after diagnosis, 227,170 (10.8%) patients had developed VTE. The Khorana score was a weak to modest predictor of the 1-year risk of VTE (area under the curve, 0.565; 95% confidence interval, 0.564-0.566). Abstract 204: Incidence of and Risk Factors for Venous Thromboembolism Among Hospitalized Patients With Cancer and COVID-19: Report From the COVID-19 and Cancer Consortium (CCC19) Registry. https://bit.ly/38waPnX. The study included 1,813 hospitalized patients with COVID-19 and cancer who were enrolled in the CCC19 registry. Patients had an increased risk of VTE if they had received anticancer therapy in the last 3 months (odds ratio, 1.63), had active disease (OR, 1.25 for stable/responding disease and 1.67 for progressing disease), had a cancer subtype with a high VTE risk (OR, 1.57 for high risk and 3.42 for very high risk), or were admitted to the ICU within 48 hours of hospitalization (OR, 2.38). Patients had a reduced risk of VTE if they received preadmission anticoagulant (OR, 0.80) or antiplatelet therapy (OR, 0.71). The researchers said this information will aid the development of a risk prediction tool for VTE in hospitalized patients with cancer and COVID-19. For more information on the CCC19 registry, listen to the Blood & Cancer episode, “Studying cancer patients with COVID-19: NCCAPS and CCC19.” https://bit.ly/39lB0x0. Abstract 206: Anticoagulant and Antiplatelet Use not Associated With Improvement in Severe Outcomes in COVID-19 Patients. https://bit.ly/3bvHqvV. This retrospective study included 28,076 patients with confirmed COVID-19 – 1,024 of whom were on antiplatelet agents, anticoagulants, or both. Chronic anticoagulant or antiplatelet use was not associated with a significantly lower risk of VTE (OR, 1.44), emergency department visit (OR, 0.94), ICU stay (OR, 0.87), or death (OR, 0.91). However, anticoagulant or antiplatelet use was associated with a decreased risk of ventilator use (OR, 0.72). Overall, these findings suggest chronic anticoagulant or antiplatelet use don't mitigate disease severity in COVID-19 patients, the researchers concluded. The session in which these abstracts were presented is entitled, “904. Outcomes Research – Non-Malignant Conditions: Venous Thromboembolism Associated With Cancer and/or COVID-19,” and details can be found here: https://bit.ly/39olwIl. Data in some of the abstracts differ from data presented at the meeting. Disclosures Dr. Sanfilippo disclosed relationships with Covington & Burling, Luther & Associates, Bayer, Health Services Advisory Group, and Amgen. Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Regina James, MD, tells her personal story and discusses how to understand health equity with guest host Carol A. Bernstein, MD. Dr. James is deputy medical director and chief of the division of diversity and health equity at the American Psychiatric Association. She also serves on the advisory board of The PACT group (Pan African Clinical Trials) and receives no income from the group. Dr. Bernstein, a past president of the APA, is vice chair for faculty development and well-being at Montefiore Medical Center/Albert Einstein College of Medicine, New York. She has no disclosures. Take-home points The Robert Wood Johnson Foundation defines health equity as: “Everyone has a fair and just opportunity to be as healthy as possible. This requires removing obstacles to health such as poverty, discrimination, and their consequences, including powerlessness and lack of access to good jobs with fair pay, quality education and housing, safe environments, and health care.” Equity embraces the idea of inclusiveness and evaluates a whole health care system instead of focusing only on individual marginalized communities. For example, it is essential to understand the social determinants that lead to groups being medically underserved and then to understand the impact of the medically underserved on the entire system. Dr. James led a 20-year career in research and leadership within the National Institutes of Health, including the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, and the Eunice Shriver National Institute of Child Health and Human Development. She later transitioned to 2M, a research consulting agency, and then to the APA. Within the APA, Dr. James has developed a 5-point strategic plan with the vision that all APA members will be culturally competent and sensitive, and able to provide mental health care for any individual regardless of age, race, gender, or sexual orientation. The strategic plan focuses on raising awareness about mental health equity and destigmatization and leveraging the expertise of the APA membership in their communities. A cornerstone of the plan is an educational agenda, including materials on health equity in psychiatry and outreach to APA members and their community partners. In addition, Dr. James and her office partner with APA leadership to lobby the government for mental health equity and inclusion. Dr. James describes structural racism as current policies within an organization that lead to racial inequalities. Separate from the Office of Diversity and Health Equity, the APA established a Presidential Task Force to Address Structural Racism Throughout Psychiatry to identify the scope and targets of structural racism within organized psychiatry, including the APA. It also seeks to identify how structural racism affects practicing psychiatrists and their patients. References Braveman P et al. What is health equity? Robert Wood Johnson Foundation. 2017 May 1. American Psychiatric Association. Diversity and health equity. American Psychiatric Association. Mental health disparities: Diverse populations. APA Presidential Task Force to Address Structural Racism Throughout Psychiatry. https://www.psychiatry.org/psychiatrists/structural-racism-task-force Rosenkranz KM et al. J Surg Education. 2020. doi: 10.1016/j.surg.2020.11.013. Simonsen KA and Shim RS. Psychiatr Clin North Am. 2019 Sep;42(3):463-71. Alves-Bradford J-M et al. Psychiatr Clin North Am. 2020 Sep;43(3):415-28. Aggarwal NK et al. Patient Educ Couns. 2016 Feb;99(2):198-209. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

In this episode, we bring you clips from the best Blood & Cancer shows of 2020. Blood & Cancer will be back with new episodes in 2021.  ESMO 2020: Late-breaking and practice-changing studies on COVID-19 and breast, lung, gastrointestinal, and other cancers https://bit.ly/3h7aWZM Beyond the lungs: How COVID-19 affects the blood, brain, gastrointestinal system, and other organ systems https://bit.ly/37GhV8Q EHA25: AML, myeloma, polycythemia vera, and COVID-19 with EHA President John Gribben https://bit.ly/3nS4592 VTE rate, 'COVID toes,' and Virchow's triad: What you need to know about COVID and coagulation https://bit.ly/3rizmnM ASCO 2020: Practice-changing studies in breast, lung, colorectal, and other cancers https://bit.ly/37EIbkg * * * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

The ASH Research Collaborative COVID-19 Registry for Hematology was established earlier this year to study patients with hematologic malignancies diagnosed with COVID-19. Now, the registry also includes patients with nonmalignant hematologic disorders and hematologic manifestations of COVID-19. William Wood, MD, of the University of North Carolina at Chapel Hill, recently presented data from the registry at the ASH Annual Meeting. In this episode, Dr. Wood tells host David H. Henry, MD, how the registry came to be and reviews some of its findings. About the registry The registry is part of the ASH Research Collaborative, an organization established in 2018 to foster collaboration to accelerate progress in hematology. The registry houses data on patients with a COVID-19 diagnosis and hematologic disorders/malignancies or hematologic manifestations of COVID-19. Health care providers around the world can contribute data to the registry. Anyone can view summaries of the deidentified data on the registry website. The website data are updated every day or every few days. The information compiled in the registry includes: The nature of patients’ underlying disease Treatments received until COVID-19 diagnosis Sociodemographic information COVID-19 symptoms and time to resolution or death COVID-19–directed treatments Expected prognosis Whether patients opted for intensive care. Registry findings The registry data presented at ASH 2020 included 656 patients with hematologic malignancies and COVID-19. Dr. Wood said the first conclusion drawn from these data is that patients with underlying hematologic malignancies are a “medically vulnerable population” when it comes to COVID-19. The mortality rate was 20% overall and 33% in patients with hospitalization-level severity. The other major finding, Dr. Wood said, is that the risk of severe COVID-19 and death is differentially distributed. Risk factors for adverse COVID-19 outcomes include: Increasing age Advanced underlying disease or limited prognosis Forgoing intensive management. Relevant links ASH Research Collaborative: https://bit.ly/37pczyV. COVID-19 Registry for Hematology: https://bit.ly/3r1U9vO. Blood Adv. 2020. 4(23):5966-75. https://bit.ly/34jWVTt. Wood W et al. ASH 2020, Abstract 215. https://bit.ly/3gRzw0A. Disclosures Dr. Wood disclosed research funding from Pfizer, consultancy for Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd  

Richa Bhatia, MD, conducts a Masterclass on how to identify medical and neurologic illnesses that present with psychiatric symptoms and mimic psychiatric diagnoses. Dr. Bhatia is a board-certified general and child and adolescent psychiatrist in private practice. She has no disclosures. Take-home points Psychiatric diagnoses are diagnoses of exclusion. Psychiatric clinicians must maintain a high level of clinical suspicion for medical and neurologic illnesses that present with psychiatric symptoms and mimic psychiatric diagnoses. When patients have a “strange” presentation of their psychiatric illness, including being out of the usual age range, a fast progression, or an unusual constellation of symptoms, clinicians should pursue a medical work-up and think broadly about other diagnoses that might mimic the psychiatric diagnosis. Dr. Bhatia provides an overview of common medical and neurologic illnesses that mimic psychiatric diagnoses, including hypothyroidism, delirium, HIV/AIDS, Addison disease, autoimmune encephalitis, temporal lobe epilepsy, frontotemporal dementia, Wilson’s disease, and Parkinson’s disease. Summary Hypothyroidism is an endocrine disease that can mimic depression. The physical symptoms include constipation, edema, dry skin, hair loss, weight gain, and cold intolerance. Individuals with comorbid hypothyroidism and depression report inadequate response to antidepressants, so psychiatrists should check the patient’s thyroid-stimulating hormone or refer them to their primary care physician if they suspect hypothyroidism with elevated TSH. Delirium is a common yet underdiagnosed syndrome that occurs secondary to medical illness and can produce an array of neuropsychiatric symptoms, including psychosis, irritability, and disorganized behaviors, which can lead to misdiagnosis as schizophrenia or mania. Delirium presents as an abrupt change in cognition with disorientation and significantly impaired attention. Hypoactive delirium presents with lethargy, apathy, and decreased alertness, and is often mistaken for depression in the hospital setting. Simple beside tests such as the Confusion Assessment Method can be used to quickly aid in diagnosing delirium. HIV/AIDS can mimic psychiatric disease through direct effect on the nervous system, opportunistic disease, intracranial tumors, cerebral vascular disease, and medication adverse effects. HIV can mimic depression by causing neurovegetative symptoms; apathy, psychomotor slowing, and working memory deficits are more characteristic of the neuropsychiatric impairment from HIV rather than a primary depressive disorder. In late-stage HIV/AIDS, dementia can cause bizarre behaviors, delusions, and mood disturbance such as euphoria and irritability. Addison disease is characterized by low blood pressure, hyperpigmentation, nausea, vomiting, weakness, fatigue, hypokalemia, and hyponatremia. Addisonian crisis can present with neuropsychiatric symptoms of delirium, anxiety, agitation, cognitive impairment, and auditory and visual hallucinations. Autoimmune encephalitis, with anti–N-methyl-D-aspartate receptor encephalitis as the most common type, often masquerades as a primary psychotic symptom. Notable symptoms include subacute onset with fast progression and no clear prodrome, working memory impairment, agitation, or lethargy. Other presenting symptoms include focal neurologic deficits, new-onset or rapidly developing catatonia, fever, headaches, flu-like illness, and autonomic disturbance. Temporal lobe epilepsy also can mimic a primary psychiatric disorder. The symptoms of seizure-like staring, blinking, lip-smacking, and behavioral arrest are precipitated by a sensation of fear or epigastric sensation and depersonalization, which can lead to misdiagnosis as a panic attack. Frontotemporal dementia (FTD) can be mistaken for a primary psychiatric diagnosis in the initial stages. Hallmark symptoms include progressive behavioral change with disinhibition and a decline in executive functioning and language skills such as verbal learning and reasoning. FTD is the second most common dementia in people aged younger than 65 years. Patients with FTD struggle to give a history, and often lack a psychiatric history or exposure to psychotropic drugs. Clinicians should maintain a high degree of clinical suspicion for FTD in new-onset psychiatric syndromes in older individuals. Stroke can lead to poststroke depression and anxiety, apathy, emotional lability, and personality changes. Depression after stroke, occurring hours to days after the insult, is associated with greater cognitive impairment and increased mortality. The diagnosis of poststroke depression is challenging because of impairments in language and cognition after stroke. Apathy can occur separately from depression and diminish recovery. Wilson’s disease results in copper deposits in the brain and liver. The psychiatric symptoms, including psychosis, occur before neurologic changes. Parkinson’s disease also can result in depression-like symptoms, given the motor and neurovegetative symptoms from the neurodegeneration. Fatigue, psychomotor slowing with diminished facial expression, postural changes, and sleep disturbance are common conditions that can mimic depression. References  Carroll VK. Current Psychiatry. 2009 Aug;8(8):43-54. Welch KA and Carson AJ. Clin Med (Lond). 2018 Feb;18(1):80-7. Scarioni M et al. Ann Neurol. 2020;87(6):950-61. Evans DL et al. Neuropsychiatric manifestations of HIV-1 infection and AIDS, in “Neuropsychopharmacology: 5th Generation of Progress.” Philadelphia: Lippincott Williams & Wilkins, 2002, pp. 1281-99. Deng P and Yeshokumar A. Psychiatric Times. 2020 Jan. (37):1. Kumar A and Sharma S. Complex partial seizure, in “StatPearls [Internet].” Treasure Island, Fla.: StatPearls Publishing, 2020 Jan. (Updated 2020 Nov 20). Rao V. Neuropsychiatry of stroke. Geriatric Workforce Program. Johns Hopkins Medicine. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com        

A pair of biomarkers are being used to guide treatment and predict mortality in patients with graft-versus-host disease (GVHD), according to James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York. In this episode, Dr. Ferrara explains how measuring these biomarkers – REG3-alpha and ST2 – can prevent over- and undertreatment of acute GVHD. The biomarkers have also been shown to predict nonrelapse mortality more accurately than a change in clinical symptoms. Before reviewing these findings, Dr. Ferrara tells host David H. Henry, MD, what GVHD is, how to recognize it, and how it’s typically treated. GVL and GVHD GVHD is “very tightly associated” with the graft-versus-leukemia (GVL) effect, Dr. Ferrara explained. The GVL effect refers to the ability of donor immune cells to eliminate host malignant cells after allogeneic hematopoietic stem cell transplant (allo-HSCT). The donor T cells respond to minor histocompatibility antigens on malignant cells but also on normal cells. When the donor T cells attack the normal cells, the patient develops GVHD. To prevent GVHD, patients may receive cyclosporin, tacrolimus, methotrexate, sirolimus, or other drugs in various combinations. Despite prophylaxis, slightly under half of allo-HSCT recipients will still develop some form of GVHD, Dr. Ferrara said. Acute GVHD Acute GVHD typically occurs in the first month or two after transplant, and about 50% of cases happen in the first month, Dr. Ferrara said. There are three primary targets – the skin, liver, and GI tract. The rash observed with skin GVHD is vesiculopapular, and the extent of the rash determines the stage of GVHD in the skin. Increase in total bilirubin is used to measure the stages of liver disease. GVHD in the GI tract is characterized by persistent nausea and vomiting or diarrhea (up to liters a day). Evaluating the skin, liver, and GI tract together can provide the overall GVHD grade, between 1 and 4. Grade 4 GVHD is the most severe, and grade 1 is a skin rash that usually affects less than 50% of the body surface area. Over- and undertreatment When GVHD is mild and limited to the skin, topical steroid creams are adequate treatment. When GVHD progresses into the GI tract and liver, patients require systemic immunosuppression. However, it’s difficult to tell whether GVHD is going to be mild, moderate, or severe. So when patients with acute GVHD receive systemic steroids at a starting dose of 1 mg/kg, many of these patients are overtreated “and a fair number of them are undertreated because we don't actually know which patients are going to progress and which patients are going to respond to treatment,” Dr. Ferrara said. He noted that the JAK1/2 inhibitor ruxolitinib was approved to treat steroid-refractory acute GVHD last year. Prior to that, the only approved treatment for GVHD was systemic steroids. Biomarkers signal disease severity Through their research, Dr. Ferrara and colleagues identified two biomarkers of GVHD severity – REG3-alpha and ST2. “When the GI tract is damaged early, these proteins flood into the systemic circulation, and they can actually tell us who's got a damaged GI tract very early, even before one has symptoms like diarrhea,” Dr. Ferrara explained. The biomarkers can be used to assess, at the onset of GVHD, whether or not a patient has crypt damage and needs more intensive treatment. Biomarkers guide treatment, predict outcomes Dr. Ferrara and colleagues used serum samples collected by the Mount Sinai Acute GVHD International Consortium (MAGIC) to develop MAGIC Algorithm Probability (MAP). MAP is calculated from patients’ levels of REG3-alpha and ST2 and can be used to predict the risk of severe GVHD. “You put these two biomarkers into an equation, you get a single number, and that number tells you whether [the patient is] high risk, low risk, or intermediate risk,” Dr. Ferrara explained. He and his colleagues found they could use MAP to predict patients’ response to treatment and mortality. In fact, MAP was able to predict nonrelapse mortality more accurately than a change in clinical symptoms (Blood Adv. 2019. 3[23]:4034-42. https://bit.ly/39QNUVn). Standard practice, ongoing trials MAP is increasingly becoming a part of standard practice, Dr. Ferrara said. A company called Viracor Eurofins Clinical Diagnostics licensed MAP and provides tests for consumer use (https://bit.ly/33RhRBa). Centers can send blood samples to Viracor to test. More than 50 centers in the United States sent at least 1,000 samples to Viracor for testing in 2019, Dr. Ferrara said. He and his colleagues are also utilizing MAP in ongoing clinical trials: A phase 2 study of natalizumab plus standard steroid treatment for high-risk acute GVHD (NCT02133924; https://bit.ly/3grvsUK). A pilot trial of alpha1-antitrypsin for preemption of steroid-refractory acute GVHD (NCT03459040; https://bit.ly/3qy48c9). A phase 2 trial of itacitinib for low-risk GVHD (NCT03846479; https://bit.ly/37GkaYK). Disclosures: Dr. Ferrara has a patent for serum biomarkers of acute GVHD and receives royalties from Viracor. Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd  

Eliza W. Menninger, MD, spoke with Psychcast host Lorenzo Norris, MD, about how to help patients deal with anxiety related to the COVID-19 pandemic. Dr. Menninger is medical director of the behavioral health partial hospital program at McLean Hospital in Belmont, Mass. She treats patients with major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Dr. Menninger also treats patients in McLean’s Schizophrenia and Bipolar Disorder Outpatient Clinic. She has no disclosures. Dr. Norris has no disclosures. Take-home points Anxiety related to stress, fear, worry, and grief has spiked in all phases of the pandemic. Initially, we faced uncertainty not knowing how to adapt to restrictions, and we assumed that the adaptations would be short term. Six months into the pandemic, we’ve moved into questions about maintaining these adaptive processes over the long term. As the medical director of a partial hospitalization program, Dr. Menninger created an acronym, “MASK,” to help people cope with the stress of the pandemic. MASK stands for Make boundaries, Avoid the virus, Stay connected, Keep the faith. Summary Making boundaries refers to encouraging people to use similar behaviors from their past routines to maintain normalcy. For example, for people who work from home, Dr. Menninger suggests getting dressed and ready for work as though you’re actually going, and taking breaks from screens to reduce virtual platform fatigue. People are feeling socially and physically restricted by the pandemic, and she emphasizes going outside regularly. Boundaries that help delineate physical spaces and emotional responsibilities can alleviate the physical and mental clutter that compounds stress. Avoiding the virus is a constant chore, so Dr. Menninger came up with a humorous song aimed at helping her patients remember their role in avoiding exposure to the coronavirus. Staying connected means focusing on the social connection and feeling the presence of the other person instead of just sensing the temporary connection provided through the virtual platform. Dr. Menninger suggests imagining that the person with whom you’re connecting is in the room with you. Self-care through maintaining routines; exercising; maintaining healthy nutrition; seeking out humor; and enjoying art, music, and other stimuli helps people connect with themselves and others. Keeping the faith means remembering that the pandemic will end, and we have the tools to build resilience in ourselves and patients. Dr. Menninger finds hope in the way her clinical staff has been creative to make a difference in the patients’ life amid the constant changes. She and Dr. Norris cite examples of patients using creativity to overcome overwhelming life circumstances, build on their strengths, and reframe the pandemic to find the silver lining. Reference Marcus PH et al. Current Psychiatry. 2020 Dec;19(12):28-33. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Researchers are conducting the first U.S. trial of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for the treatment of peritoneal carcinomatosis in patients with gynecologic or gastrointestinal cancers. Coprincipal investigator Thanh H. Dellinger, MD, of City of Hope in Duarte, Calif., describes this trial and the PIPAC procedure to host David H. Henry, MD, in this episode. To start, the pair discuss a patient who might be eligible for PIPAC – one with stage 3 ovarian cancer. General approach to stage 3 ovarian cancer Therapy typically includes a combination of surgery and chemotherapy. The order in which chemotherapy is given, either pre- or postoperatively, depends on performance status and whether patients have extra-abdominal disease or parenchymal liver disease. Operative approaches, including debulking surgery, are pursued if believed to be optimal, meaning all gross residual disease can be resected. If all residual disease cannot be resected, patients are offered neoadjuvant chemotherapy, typically for three to four cycles before an interval debulking surgery, followed by postoperative adjuvant chemotherapy. Intraperitoneal chemotherapy Intraperitoneal (IP) chemotherapy is used to treat peritoneal surface malignancies. The peritoneum is a separate organ that is difficult to treat adequately with intravenous chemotherapy alone. Giving IP chemotherapy in combination with intravenous chemotherapy may be more effective than intravenous chemotherapy alone (N Engl J Med. 2006; 354:34-43; https://bit.ly/3g3lngx). However, there are many challenges in delivering IP chemotherapy, including increased side effects of abdominal pain and IP catheter failure. Recent clinical trials have shown that, with the addition of bevacizumab, the survival benefit with IP chemotherapy may not be as significant as prior trials suggested (J Clin Oncol. 2019 Jun 1;37[16]:1380-90; https://bit.ly/2VAmRVW). In general, IP chemotherapy has not been embraced by the medical oncology community as much other types of chemotherapies, Dr. Dellinger said. What is PIPAC? PIPAC is a novel therapy discovered by a German surgical oncologist, Marc A. Reymond, MD, from University of Tuebingen (Germany). PIPAC delivers chemotherapy at a reduced dose directly into the intraperitoneal cavity but in a pressurized and aerosolized form. PIPAC is done at the time of the diagnostic laparoscopy and requires a nebulizer for aerosolization of the chemotherapy as well as a high-pressure injector. This approach allows for the chemotherapy to be pushed deeper into tissues, compared with hyperthermic intraoperative peritoneal chemotherapy (HIPEC). With HIPAC, tissue penetration is typically 1 mm or less. With PIPAC, there is deeper penetration and better distribution of chemotherapy throughout the entire intraperitoneal cavity. With PIPAC, chemotherapeutic agents are given at a lower dose than is typically administered with IP or intravenous chemotherapy, which helps in reducing the toxicity. PIPAC is given every 6 weeks for three cycles, requiring three laparoscopic procedures. These laparoscopic procedures allow for the opportunity to obtain peritoneal tumor biopsies before and after to investigate the natural course of these tumors and their microenvironment. Toxicity of PIPAC PIPAC has been done in more than 800 patients with gastrointestinal and gynecologic cancers in Europe and Asia. Severe adverse events  have been minimal, with about 12%-15% grade 3/4 SAEs and very rare grade 5 SAEs. The most common side effect is typically abdominal pain, attributed to the IP administration in conjunction with the laparoscopic surgery. Renal toxicity is a concern with intravenous cisplatin use, but this has not yet been seen with PIPAC. With PIPAC, cisplatin is given at 10.1 mg/m2 and doxorubicin is given at 2.1 mg/m2, doses that are much lower than the typical doses for these drugs. PIPAC in clinical trials PIPAC clinical trials have moved into phase 2 in Europe for ovarian cancer, with a publication demonstrating an objective response rate of over 60% in platinum-resistant ovarian cancer (Gynecol Oncol. 2015 May;137[2]:223-8; https://bit.ly/2KY701r). A phase 3 trial of PIPAC was planned but was stalled because of the COVID-19 pandemic. Because of the need for Food and Drug Administration approval, researchers have just launched the first phase 1 trial of PIPAC in the United States. Phase 1 trial of PIPAC City of Hope is working with affiliates at Mayo Clinic in Jacksonville, Fla.; Northwell Health in New York; and the National Institutes of Health to enroll eligible candidates for a phase 1 trial (NCT04329494; https://bit.ly/3qs8H7U). Eligible candidates include those with gastric, uterine, colorectal, appendiceal, and ovarian cancer with evidence of peritoneal carcinomatosis who have failed at least one line of therapy. PIPAC is an outpatient procedure, but given the trial and need for monitoring, patients typically leave the hospital the following day after blood samples are obtained for the study. City of Hope has recruited seven patients since activating their study in August 2020, with a goal of enrolling 16 patients by spring 2021. Future directions Peritoneal tumor biopsies obtained during the laparoscopic procedures are being used to study the microenvironment of these cancers. In eventual phase 2 clinical trials, the researchers may include immune checkpoint inhibitors. Biomarker analyses are underway, looking at expression of PD-1 and tumor-infiltrating lymphocytes. The researchers are also studying the role of genomic sequencing and DNA repair. Disclosures: Dr. Dellinger and Dr. Henry have no financial disclosures relevant to this episode. Show notes by Sheila De Young, DO, resident at Pennsylvania Hospital, Philadelphia. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Oliver Freudenreich, MD, talks with Lorenzo Norris, MD, about principles of pandemic management among patients with serious mental illness. Dr. Freudenreich reported receiving grant or research support from Alkermes, Avanir, Janssen, and Otsuka. He has served as a consultant to the American Psychiatric Association, Alkermes, Janssen, Neurocrine, Novartis, and Roche. Dr. Norris has no disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com  

In this episode, host David H. Henry, MD, highlights some recent articles from Blood, the Journal of Clinical Oncology, and the New England Journal of Medicine. Blood How I Treat series on hematologic complications in pregnancy. https://bit.ly/3fr5nV8 Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. https://bit.ly/3nQvhF6 Journal of Clinical Oncology Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. https://bit.ly/3maTOE4 Related Blood & Cancer episode: Cancer and hepatitis B virus: ASCO's recommendations for HBV screening, monitoring for reactivation, and how to treat patients. https://bit.ly/3m0jjrF Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy. https://bit.ly/372FFCB Chemotherapy and COVID-19 Outcomes in Patients With Cancer. https://bit.ly/35WRLOi Related Blood & Cancer episodes: Studying cancer patients with COVID-19: NCCAPS and CCC19. https://bit.ly/3pYl2Au TERAVOLT registry sheds light on patients with thoracic cancers and COVID-19. https://bit.ly/2URdwJh Diffuse Large B-Cell Lymphoma’s New Genomics: The Bridge and the Chasm. https://bit.ly/36XdGnY New England Journal of Medicine Osimertinib in Resected EGFR-Mutated Non–Small Cell Lung Cancer. https://bit.ly/2J5q7FQ Humoral Immune Response to SARS-CoV-2 in Iceland. https://bit.ly/2USw7ET Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. https://bit.ly/39aM0ia Remdesivir for the Treatment of COVID-19 – Final Report. https://bit.ly/375dYJk Remdesivir for 5 or 10 Days in Patients with Severe COVID-19. https://bit.ly/2IZJ7Wq Disclosures: Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

This week, we revisit four shows that offer guidance to clinicians for addressing the mental health fallout from COVID-19. Lisa W. Coyne, PhD, founder of the McLean OCD Institute for Children and Adolescents in Belmont, Mass., focuses on helping children and adolescents with anxiety and obsessive-compulsive disorder. She disclosed receiving royalties from New Harbinger and Little Brown Publishing. Christine Moutier, MD, describes interventions that can prevent patients from ending their lives by suicide. She is chief medical officer of the American Foundation for Suicide Prevention. Dr. Moutier reported no disclosures. Sanjay Gupta, MD, offers a Masterclass on how to determine which medication works best for geriatric patients with symptoms of dementia. Dr. Gupta, chief medical officer at BryLin Hospital in Buffalo, N.Y., disclosed serving on the speakers’ bureaus of AbbVie, Acadia, Alkermes, Intra-Cellular Therapies, Janssen, and Otsuka. Peter Yellowlees, MBBS, MD, wraps up the podcast with perspective about permanent changes that could be in the offing to the practice of psychiatry because of the pandemic. He is a professor of psychiatry at the University of California, Davis. Dr. Yellowlees has no disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Diana M. Martinez, MD, conducts a Masterclass on marijuana’s effects on psychiatric disorders. Dr. Martinez, a professor of psychiatry at Columbia University, New York, specializes in addiction research. She disclosed receiving medication (cannabis) from Tilray for one study and has no other financial relationships with this company. Take-home points The use of cannabis, recreationally and medically, has been a controversial topic for ages, and the classification of cannabis as a schedule I controlled substance has made it all the more difficult to research and meaningfully understand its harms and benefits. Based on information from the National Academies of Sciences publication Health Effects of Marijuana: An Evidence Review and Research Agenda, Dr. Martinez presents a sweeping overview of the role of cannabis in two domains: Its ability to worsen psychiatric symptoms, and its role in causing psychiatric disorders. The cannabis plant has 100 cannabinoids. The two most commonly studied are tetrahydrocannabinol (THC), which creates the "high," and cannabidiol (CBD), which does not create a high and has many subjective effects. Cannabis is researched and used in several forms, including the smoked plant or flower form, and prescription cannabinoids based on THC – namely dronabinol (Marinol), nabilone (Cesamet), and CBD. Research suggests that both benefits and risks are tied to using cannabis and cannabinoids. Clinicians should have rational discussions with their patients about the use of cannabis. If patients are no longer responding to psychiatric treatment, and the clinician wants to talk about their cannabis use, it is important to understand the common reasons patients use cannabis, including for chronic pain, anxiety, and insomnia. Benefits There is substantial evidence supporting the use of cannabis and cannabinoids for the treatment of chronic pain. Most studies evaluated the smoked or vaporized form. Research suggests a dose of 5-20 mg of oral THC is about as effective as 50-120 mg of codeine, although there are few head-to-head studies to reinforce this finding. Cannabis will likely have a role in the pain treatment armamentarium. The risks of use include intoxication and development of an addiction. Cannabinoids may have a role in achieving abstinence from addiction to cannabis and other substances. THC in the form of cannabinoids shows some promise for its use in disorders such as PTSD and obsessive-compulsive disorder, but larger controlled studies are needed. In addition, cannabinoids have an effect when combined with other behavioral interventions, such as exposure therapy. Risks There is substantial evidence that cannabis has a moderate to large association with increased risk of developing psychotic spectrum disorders in a dose-dependent fashion, particularly in patients who are genetically vulnerable. Moderate evidence suggests that cannabis causes increased symptoms of mania and hypomania in people with bipolar disorder who use it regularly. Cannabis can cause addiction. About 9% of people who use it will develop a substance use disorder, and the risk of developing a substance use disorder increases to 17% in people who start using cannabis in their teenage years. Frequent cannabis use is associated with withdrawal symptoms, such as irritability, sleep problems, cravings, decreased appetite, and restlessness. References National Academies of Sciences, Engineering, and Medicine. Health Effects of Marijuana: An Evidence Review and Research Agenda. Washington, DC: National Academies Press, 2017. Whiting PF et al. JAMA. 2015;313(24):2456-73. Fischer B et al. Am J Public Health. 2017 Jul 12. doi: 10.2105/AJPH.2017.303818. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com  

In this episode, we discuss updated guidelines on the screening and management of hepatitis B virus (HBV) in patients about to start anticancer therapy. The guidelines come from an American Society of Clinical Oncology Provisional Clinical Opinion (PCO) published earlier this year. Jessica P. Hwang, MD, of MD Anderson Cancer Center, and Andrew Artz, MD, of City of Hope, are cochairs of the ASCO PCO. They joined host David H. Henry, MD, to discuss the guidelines. Epidemiology of HBV Data suggest chronic HBV infection affects 257 million people globally. In the United States, chronic HBV infection has a prevalence of less than 1%, but the prevalence of past HBV can be 5%-40% in high-risk populations. High-risk populations include people born in endemic areas (i.e., Africa, Asia, and South America), those with injection drug use, men who have sex with men, and people with household contacts who have HBV. In patients with cancer, the prevalence of past HBV infection is 5%-10%, with a 0.5% prevalence of chronic HBV. HBV and oncology: Who should be screened? The ASCO PCO recommends universal HBV screening in all patients planning or undergoing anticancer therapy. To screen, practitioners should order three tests before initiating anticancer therapy: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and hepatitis B surface antibody (anti-Hbs). Interpretation of serology Chronic infection: HBsAg (+), anti-HBc (+), anti-HBs (-). Resolved past infection: HbsAg (-), anti-HBc (+), anti-HBs (+). Past infection, isolated core: HbsAg (-), anti-HBc (+), anti-HBs (-). Vaccine-induced immunity: HbsAg (-), anti-HBc (-), anti-HBs (+). Recommended treatment and/or monitoring Once a patient is infected, the HBV incorporates into the host genome and can live latently, so the patient is at risk of reactivation with immunosuppressive anticancer therapy (with chronic or past infection). Certain therapies pose a heightened risk of HBV reactivation, including anti-CD20 monoclonal antibodies and stem cell transplant. Patients receiving checkpoint blockade immunotherapy should be monitored closely for reactivation, though autoimmune hepatitis and high-dose steroids used in treating immune-related events could confound the reactivation of HBV. Further guidelines specific to checkpoint blockade immunotherapy are dichotomized and can be found in the ASCO PCO. In patients with chronic HBV infection receiving any systemic anticancer therapy, the ASCO PCO recommends antiviral prophylactic therapy during anticancer therapy and for a minimum of 12 months after anticancer therapy, with consultation of an HBV specialist. Entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide are well tolerated and have a low rate of viral resistance, making them favorable for patients who need to be treated. Implementing a screening program Recommend a multidisciplinary team approach, including physicians, pharmacists, and public health professionals. Utilize EHRs to incorporate alerts for screening and embedding screening into order sets. Ensure that positive test results are delivered to the appropriate medical team. Link patients into care for treatment and/or monitoring. Source and resources The ASCO PCO was published in the Journal of Clinical Oncology: https://bit.ly/3pClNPo. Additional resources are available on the ASCO website: https://bit.ly/35E0nt0. An infographic is also available: https://bit.ly/3pBuE3K. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Hwang disclosed relationships with Gilead Sciences, Merck Sharp & Dohme, and the Asian Health Foundation. Dr. Artz disclosed research funding from Miltenyi Biotec. Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

Lisa W. Coyne, PhD, spoke with Psychcast host Lorenzo Norris, MD, about strategies that can be used to help children and adolescents deal with anxiety and obsessive-compulsive disorder amid COVID-19. Dr. Coyne, a clinical psychologist, is founder of the McLean OCD Institute for Children and Adolescents in Belmont, Mass. She also is director with the New England Center for OCD and Anxiety in Cambridge, Mass. Dr. Coyne disclosed receiving royalties from New Harbinger and Little Brown Publishing. Dr. Norris has no disclosures. Take-home points Much of the anxiety experienced by some children and adolescents is caused by uncertainty about the future. Some children and adolescents also are watching cases of COVID-19 tick up across the country and are concerned about the mixed messages they are receiving from adults. Different cultures exist around belief in science. Rates of anxiety in general are on the rise as are demands for more mental health services. Clinicians are supporting each other to support their patients. Anxiety in young patients might present as disruptions in sleep and appetite. Look for an increase in oppositional behavior. Young patients with anxiety also might resist going to bed. Clinicians also are seeing increases in depressed mood and nonsuicidal self-injury. Acceptance and commitment therapy, a type of cognitive-behavioral therapy that is exposure based, is a strategy that can be used to help patients develop psychological flexibility and put distance between themselves and their thoughts. References Mazza MT with foreword by Coyne LW. The ACT Workbook for OCD: Mindfulness, Acceptance, and Exposure Skills to Live Well With Obsessive-Compulsive Disorder. Oakland, Calif.: New Harbinger Publications, 2020. Allmann AE et al. Acceptance and commitment therapy-enhanced exposures for children and adolescents. Exposure Therapy for Children and Adolescents with Obsessive-Compulsive Disorder: Clinician’s Guide to Integrated Treatment. Academic Press, 2020. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

Yuan Chang Leong, PhD, spoke with Psychcast host Lorenzo Norris, MD, about his research into the neural underpinnings of right- and left-leaning individuals. Dr. Leong is a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley. He has no disclosures. Dr. Norris has no disclosures. Take-home points Dr. Leong and colleagues looked for further evidence of “neural polarization,” which is defined as divergent brain activity based on conversative versus liberal political attitudes. The prefrontal cortex is the part of the frontal lobe responsible for executive and higher-order brain function that makes sense and organizes what a person is seeing, hearing, and experiencing. Participants were shown news clips about immigration policy and their brain activity showed differences in activity of their dorsomedial prefrontal cortex (DMPFC), which is active in interpreting narrative content. The findings suggest there is a neural basis for the way in which individuals with different political attitudes interpret political information and news. The research suggests that words related to threat, morality, emotions, anger, and differentiation/community drive neural polarization. Summary Dr. Leong and colleagues asked participants to watch news clips about immigration policy while undergoing functional MRI with the goal of identifying the neural correlates of neural polarization, which is thought to parallel the behavioral aspects of political polarization. Dr. Leong and colleagues identified an association of divergence in connectivity to the DMPFC to the ventral striatum, a structure involved in reward processing and sensing the valence and tone of information. Their study, published in the Proceeding of the National Academy of Sciences, suggests that information from the ventral striatum is transmitted differently to the DMPFC between groups. The findings suggest that our political beliefs might influence our interpretation of other information, as the DMPFC helps humans interpret narrative content. Dr. Leong pointed out that this study provides evidence about why it is so difficult to bridge the partisan divide. He also discussed the psychology of social identity theory and how any categorization of people makes individuals think along the lines of in-group and out-group, and how the human drive is to protect the in-group. References Leong YC et al. PNAS. 2020 Oct 20. doi: 10.1073/pnas.2008530117. McLeod S. Social identity theory. Simply Psychology. Updated 2019. University of Texas, Austin. Ethics unwrapped. In-group/out-group (video). Brooks M. Brain imaging reveals a neural basis for partisan politics. Medscape.com. 2020 Oct 27. *  *  * Show notes by Jacqueline Posada, MD, associate producer of the Psychcast; assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University, Washington; and staff physician at George Washington Medical Faculty Associates, also in Washington. Dr. Posada has no conflicts of interest. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com

In this episode, we review the latest guidelines on antiemetics from the American Society of Clinical Oncology (ASCO). Host David H. Henry, MD, is joined by ASCO guideline author Paul J. Hesketh, MD, of Lahey Hospital and Medical Center in Burlington, Mass. Dr. Hesketh explains the recommendations for antiemetic use in cancer patients receiving checkpoint inhibitors (CPIs) or high-, moderate-, or low-emetic-risk antineoplastic agents. Checkpoint inhibitors The update to ASCO’s guidelines was primarily driven by questions about antiemetic use in patients receiving CPIs, according to Dr. Hesketh. After a literature review, Dr. Hesketh and coauthors concluded that: Patients receiving CPIs alone do not require an antiemetic regimen. When CPIs are given with chemotherapy, there is no need to modify the antiemetic regimen. Dexamethasone does not compromise the efficacy of CPIs. High-emetic-risk antineoplastic agents Adults treated with cisplatin and other high-emetic-risk single agents should be offered a four-drug combination: an NK1 receptor antagonist, a serotonin (5-HT3) receptor antagonist, dexamethasone, and olanzapine on day 1. Dexamethasone and olanzapine should be continued on days 2-4, as cisplatin can cause delayed emesis. Adults treated with an anthracycline plus cyclophosphamide should be offered a four-drug combination: an NK1 receptor antagonist, a 5-HT3 receptor antagonist, dexamethasone, and olanzapine on day 1. Unlike with cisplatin, only olanzapine should be continued on days 2-4. Olanzapine is an effective antiemetic in a number of settings, Dr. Hesketh said. For example, olanzapine is useful in the setting of hematopoietic stem cell transplant. A 5-mg dose of olanzapine has proven effective and may be better tolerated than a 10-mg dose. Moderate-emetic-risk antineoplastic agents Adults treated with higher-dose carboplatin (area under the curve ≥4 mg/mL per min) should be offered a three-drug combination: an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone on day 1. Adults treated with moderate-emetic-risk antineoplastic agents (excluding higher-dose carboplatin) should be offered a two-drug combination: a 5-HT3 receptor antagonist and dexamethasone on day 1. Adults treated with cyclophosphamide, doxorubicin, oxaliplatin, and other moderate-emetic-risk antineoplastic agents known to cause delayed nausea and vomiting may be offered dexamethasone on days 2-3. Low-emetic-risk antineoplastic agents Adults treated with low-emetic-risk antineoplastic agents (e.g., fluorouracil, gemcitabine) should be offered a single dose of a 5-HT3 receptor antagonist or a single 8-mg dose of dexamethasone before antineoplastic treatment. Cannabinoids There is no good data on the use of cannabinoids, apart from those cannabinoids approved by the Food and Drug Administration, according to Dr. Hesketh. The ASCO guidelines state: There is insufficient evidence to make a recommendation regarding medical marijuana to prevent nausea and vomiting in cancer patients receiving chemotherapy or radiation. Similarly, there is insufficient evidence to make a recommendation on the use of medical marijuana in place of the approved cannabinoids dronabinol and nabilone for the treatment of nausea and vomiting in cancer patients receiving chemotherapy or radiation. SOURCE: Hesketh PJ et al. J Clin Oncol. 2020 Aug 20;38(24):2782-97. https://bit.ly/3oxahUP Show notes written by Alesha Levenson, MD, a resident at Pennsylvania Hospital, Philadelphia. Disclosures: Dr. Hesketh disclosed institutional research funding from AstraZeneca and F. Hoffmann-La Roche. Dr. Henry has no relevant disclosures. * * * For information on the negative effects of marijuana, listen to our sister podcast, Psychcast, on MDedge (https://bit.ly/3mBM6TB), Spotify (https://spoti.fi/3mwVvvn), or wherever you get your podcasts. * * * For more MDedge Podcasts, go to mdedge.com/podcasts. Email the show: podcasts@mdedge.com. Interact with us on Twitter: @MDedgehemonc. David Henry on Twitter: @davidhenrymd.

Christine Moutier, MD, joins Lorenzo Norris, MD, to discuss how clinicians can scale up interventions to reduce suicide rates amid the pandemic. Dr. Moutier is chief medical officer of the American Foundation for Suicide Prevention. She reported no disclosures. Dr. Norris also reported no disclosures. Take-home points Death by suicide is a health outcome, which means that there is always a place to intervene, whether clinically, socially, or through research. Risks for suicide during the pandemic are known to increase; however, it is not a foregone conclusion that suicide deaths will rise during or afterward. Mental health diagnoses are a risk factor for suicide, and there will be interplay with stressors such as unemployment, financial stress, grief, and socioeconomic disparities. The basics of suicide prevention include screening for suicidal ideation at behavioral health appointments. If a change in risk is identified, clinicians should use a patient-centered intervention, such as a safety plan. Summary The U.S. suicide rate has risen by 35% from 1999 to 2018, and the rates of suicide are particularly increasing in middle-aged populations as well as among youths of color. Evidence-based efforts are underway to mitigate suicide deaths through national suicide prevention plans. Yet, everyone has a role to play in suicide prevention, since part of prevention includes reducing stigma related to conversations about mental health and asking about crises and suicidal thoughts. In behavioral health settings, routine screening should be implemented for suicidal ideation and deterioration in any aspect of mental health. Asking about suicidal ideation is the bare minimum, and not all patients will admit to suicidal ideation when asked. Other risk factors for suicide include acute stressors such as decompensation and losses of relationships and employment. Most individuals with suicidal thoughts do not need to be psychiatrically hospitalized. Suicidal thoughts, as symptoms of a mental illness, can be treated with interventions other than hospitalization. The goal is to maintain safety and respond appropriately. In-office interventions include creating a safety plan or adding to an existing plan. As a silver lining, the pandemic has normalized conversations about mental health and reduced stigma around mental health experiences. Dr. Moutier discusses how, as the pandemic set in, the AFSP experienced a notable increase in requests for education about mental health and suicide prevention. References Moutier C. JAMA Psychiatry. 2020 Oct 16. https://bit.ly/34AF0Zq. Chung DT et al. https://bit.ly/31RYxm9. American Foundation for Suicide Prevention:  https://bit.ly/2HK3S8j Policy priorities: https://bit.ly/37IvO78 Safety plan worksheet: https://bit.ly/2HK3Vkv Centers for Disease Control and Prevention suicide risk factors: https://bit.ly/3jyMu3i *  *  * Show notes by Jacqueline Posada, MD, who is associate producer of the Psychcast and consultation-liaison psychiatry fellow with the Inova Fairfax Hospital/George Washington University program in Falls Church, Va.  Dr. Posada has no conflicts of interest. For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com