Wendy Stead

Clinically significant adverse events from a drug interaction between quetiapine and atazanavir-ritonavir in two patients.

Clinicians caring for patients infected with the human immunodeficiency virus (HIV) and diagnosed with psychiatric comorbidities must be aware of potential drug‐drug interactions, particularly with protease inhibitor‐based antiretroviral therapy. Although possible interactions can be predicted based on a drugs pharmacokinetic parameters, the clinical significance is often unknown. We describe two patients who experienced serious quetiapine adverse effects potentially mediated through an interaction with ritonavir‐boosted atazanavir. The first patient was a 57‐year‐old man with HIV and bipolar disease who developed rapid and severe weight gain when quetiapine was added to a stable atazanavir‐ritonavir‐based antiretroviral regimen. After the patient discontinued both quetiapine and ritonavir, his weight returned to its baseline value. The second patient was a 32‐year‐old woman with HIV, anxiety disorder, and a history of intravenous drug abuse who developed increased sedation and mental confusion when an atazanavir‐ritonavir‐based antiretroviral regimen was added to her stable antianxiety drug regimen, which included quetiapine. Her symptoms resolved promptly after discontinuation of the quetiapine. Use of the Naranjo adverse drug reaction probability scale indicated that the adverse effects experienced by the two patients were possibly related and probably related, respectively, to an interaction between quetiapine and atazanavir‐ritonavir. Quetiapine is primarily metabolized by cytochrome P450 (CYP) 3A4, and ritonavir is a potent inhibitor of CYP3A4. Thus, it is reasonable to theorize that quetiapine concentrations will increase when these drugs are used concurrently, which would be the likely cause of the toxicities in these two patients. To our knowledge, these are the first published reports of a clinically significant interaction between atazanavir‐ritonavir and quetiapine. Clinicians should be aware of the potential for this interaction, and extreme caution should be used when prescribing quetiapine and other atypical antipsychotic agents in HIV‐positive patients who are receiving antiretroviral therapy.

Meeting the needs of the resident trainee during an elective subspecialty rotation.

Objective To examine and compare perceptions between resident-trainees and faculty-educators on goals and reasons why resident trainees choose certain subspecialty elective rotations. Methods In June 2013 residents and faculty-educators at a large tertiary care academic medical center were surveyed regarding perceived resident goals for subspecialty electives. Each group was sent a different electronic survey of parallel questions assessing agreement on an ordered scale with statements about which factors impacted resident choice. Results The survey was sent to 154 residents and had 75 (49%) respondents, as well as 20 faculty-educators with 12 (60%) respondents. Residents and faculty did not differ in their responses that electives were chosen to fill perceived knowledge gaps (exact Cochran-Armitage p = .51). However, educators and residents significantly varied in the degree to which they thought resident choice was based on networking within the field (exact Cochran-Armitage p = .01), auditioning for fellowship (exact Cochran-Armitage p < .01), or exploring career options (exact Cochran-Armitage p = .01), with educators overestimating the degree to which these impacted resident choice. Conclusions Resident trainees and faculty educators agree that subspecialty electives are most frequently chosen in order to meet resident educational goals, highlighting the importance of developing and delivering high quality subspecialty curricular content for the internal medicine resident learner during electives. Many residents choose electives for career development reasons, but faculty educators overestimate this motivation.

Rosemary’s Gifts

I find the poinsettia in a basket at my front door and bring it inside. I read the card: “Merry Christmas, Doctor. Love, Rosemary and Jim.” My 10-year-old son is eating breakfast at our kitchen table. “Who sent the flowers?” he asks. “They’re from one of my favorite patients,” I say. “You have favorite patients?” he asks. I can tell by the way he asks it that his child’s pure sense of fairness is disturbed. It’s like saying you have a favorite uncle or grandchild. “What does that make the rest of them?” he asks. I realize I have oversimplified my response. Maybe “favorite” is better for a pair of earrings or a flavor of ice cream. This is a more complicated feeling that has grown over years of knowing Rosemary. The memory of the phone call eight months earlier starts to play in my head. It is a Tuesday in June. Rosemary picks up the phone on the second ring. I have been struggling with the right way to give her the news, and now the moment is here. “Hello?” she says. “Hi, Rosemary. It’s Dr Stead. I have the results of your biopsy,” I say. “Is Jim there? Do you want him to listen too?” I am pretty sure asking for her husband to join the call will give away that this isn’t good news. She is 73 years old and has been my primary care patient for 13 years. While we have been managing her diabetes, lower-extremity ulcers, hypercholesterolemia, and atrial fibrillation, I have gotten to know her and her husband and her family. I know she is the heart and soul of her family. I know she is kind and strong and funny and caring. I know she has three sons of whom she is extremely proud. I know she loves her grandchildren fiercely. Over the years she has asked me to take her husband, a son, and a daughter-in-law as my patients. I know one of her granddaughters is a dancer. Because she is the type of patient who always asks, she knows my daughter dances too, and she always asks for updates at our visits. She recently had a liver mass found incidentally on computed tomography during an emergency department visit for abdominal pain. Ultrasound-guided biopsy of the mass revealed adenocarcinoma, likely of biliary origin, and I am calling to give her the news. She doesn’t miss a beat. “Hi, Doctor” she says. “He’s outside mowing the lawn. Just give me a minute to get him.” She covers the receiver, and I can hear her open a door and yell his name. “Jim! Jimmy! It’s the doctor calling!” she shouts. But he can’t hear her over the mower. I think how it was just a normal day for them, doing normal things, and I am about to take that away. “Jimmy!” she yells three more times, but he can’t hear. She picks up the receiver again. “Do you think I should take my shirt off and stand in the window?” she asks me. “That would get his attention!” And suddenly we are both laughing, a brief escape from the moment. “I bet that would work,” I say, giggling. She tries again to get his attention. “Jimmy! Jimmy!” she yells. Finally he hears her and stops the mower. A minute later he is on the other line. “Hi, Doctor,” he says, still catching his breath. “Hi, Jim,” I say. “I have Rosemary’s biopsy results. “The liver biopsy showed cancer cells,” I say. “It’s called adenocarcinoma. It looks like it came from your bile ducts, but more tests are being done to figure this out. I want you to see an oncologist as soon as possible to talk about treatment.” I pause for a moment, but they don’t speak. Uncomfortable with silence, I race to fill it with explanations of what “adeno” means and about testing for cellular markers to determine origin and why that may matter and which multidisciplinary team I want her to see and what kinds of treatments may be discussed and I realize I am talking too much. I stop. Jim starts. “Well, Doctor, that’s certainly not the news we were hoping for.” “I know,” I say. “I’m so sorry.” Rosemary stays quiet. I am uncertain about her prognosis at this point, so I try to focus on the next steps. “I think we have to take it day by day for now,” I say. “Let’s see the oncology team and hear what they have to say about the options for treating this. We’ll know more after your visit with them, and we can meet together and talk about the plan.” I warn her about the risk of cholangitis with obstruction of bile ducts, and I ask her to call me right away with any new abdominal pains, fevers, chills, or any other new symptoms. I feel like I am talking too much again. I ask if she has any other questions, but she is still silent. I remind her of the date of the scheduled oncology appointment. More silence. This time I hold my tongue with all my strength to make space for her questions, but she doesn’t have any. I am about to say good-bye when Rosemary finally speaks. “I’m so sorry you had to tell me this,” she says. “I still remember the day we met.” I’m afraid I gasp audibly. My tears are almost instant. She’s sorry for me? This is not the way it usually goes. I am the one that should be offering comfort. My experience delivering news like this is that many patients, upon receiving a terminal diagnosis, think not of themselves in those first few moments, but of all the people they love and how this difficult news will affect their loved ones. Rosemary took this A PIECE OF MY MIND

Improving communication between medical and surgical specialists using interspecialty education strategies: A mixed-methods study -

Objective: Poor communication between medical and surgical specialists negatively impacts patient care and represents a serious challenge for medical educators. The objective of this study was to measure the effect of a brief interspecialty education program on perceived communication between medical and surgical specialists at a US medical center. Methods: In 2011, an interspecialty education program (“Diagnosing Prosthetic Joint Infections”) was developed and administered by orthopaedic surgery (OS) and infectious diseases (ID) faculty to members of both divisions. The 60-minute program included a review of diagnostics followed by small mixed-group discussions about optimal diagnostic approaches. Surveys (immediately pre- and post-intervention) and a focus group (3 months post-intervention) assessed the impact of the program on interspecialty communication and collaboration. Results: Seventeen OS (41% of whom were trainees) and 13 ID (46% trainee) providers participated. Twenty-nine percent of OS and 62% of ID providers were female. Postintervention, the proportion of participants perceiving that “other” specialty providers were often “effective communicators” (p=0.014) and “effective collaborators” (p=0.025) increased. All participants believed interspecialty education would improve communication. Focus group participants perceived that the program improved interspecialty communication, organizational practice, and patient care. Conclusions: These findings demonstrate that brief interspecialty education programs can improve communication between medical and surgical specialists and could enhance patient care.

A Story I Hope Ends Up Being True

“Every person contributes,” he says. “You don’t have to join the Peace Corps to do something worthwhile. I don’t like it when her friends act like her job isn’t as important to the world as theirs.” He tells me about his 21year-old daughter. She recently graduated from college and got her first job in communications, and he’s proud of her. “Do you have kids?” he asks. He is 44 years old and battling anaplastic myeloma. I’m not sure of the precise ways in which it’s different from regular myeloma, but I know it’s bad. After two failed bone marrow transplants, he’s been admitted for salvage chemotherapy, but it has been complicated by respiratory syncytial virus and parainfluenza pneumonias and now increasing fevers with progressing pulmonary infiltrates for which his hematology team asked for infectious diseases consultation. That’s when I meet him. Our focus is to make sure there’s not a new infection here that we could treat to help him feel better; to give him some more time. My team and I interrogate him about symptoms. We ask about where he’s lived and traveled, what he’s done for work, what his hobbies are, his pets, his exposures. All the detailed minutiae of the infectious diseases social history—the careful, probing questions that sometimes hold the clues that no one else has yet uncovered. At the very least they give us a lens through which to see his life beyond all this. The one where he travels the world as an economist. The one he lives with his wife, his oldest daughter, his 4-year-old twins, and his toddler son. We recommend a few more tests, trying to balance the benefits of figuring it out vs the risks of further invasive procedures. We suggest empirical broadspectrum treatments to cover all the usual suspects, but we don’t get any new answers and his condition seems to be worsening—continued coughing, increasing infiltrates on another chest CT, new frontal lobe strokes on a head MRI done for changes in his neurologic examination. He recognizes things are not going well and asks to go home. I almost don’t see him that last day because it’s hard to face him with no answers. “Yes, I have kids,” I say, “a 12-year-old daughter and a 9-year-old son.” And that simple response opens the door. The vast space between helpless physician and suffering patient, the one where shame and disappointment can live and grow, is bridged in an instant, and for the next several precious minutes, I realize how glad I am that I came. The smells and sounds of the bone marrow transplant unit disappear, and we talk. He tells me about his twin daughters and how different they are from each other. We talk about the challenges of raising kids in the time of social media and iPhones. He explains what it means to work as an economist. I assume too simplistically that it’s all about math, but he describes it is more about theories, about “telling a story that you hope ends up being true.” “Math for me was a means to an end,” he describes, “but I never really understood math in the way a mathematician does.” I hear admiration in his voice as he describes his friend in Haiti “who has one of those minds. One that thinks and understands like a mathematician.” He makes his profession sound like one he sort of fell into “when I decided not to become a lawyer and just kept going on to get more degrees in economics,” culminating with his PhD. “There are only about 50 people in the country who do what I do,” he says, though with humility that wants you believe he chose it because there wasn’t much competition. He insists you have to be “way more brilliant” to be a doctor than an economist, but I don’t think either of us believes this. I am surprised to look at my watch and realize 20 minutes has passed. As I reluctantly become the doctor again, I ask if I can examine him and slide back into the usual routine. I listen to his lungs with my stethoscope and hear the same wet-sounding crackles and wheezes throughout his lower lobes that have been there for days ... the ones we have not been able to fix. “I hear you may get to go home soon,” I say. “Yes,” he replies, a smile spreading across his face. “Even if I’m too tired to do much, I like to just lie down and watch my kids run around.” “That sounds wonderful,” I say. “We suggested a couple of oral antibiotics to your team that they could prescribe when you leave to cover most of the usual bugs. They should help protect you while your immune system is so impaired.” As the words leave my lips I realize I am also telling a story that I hope ends up being true. He seems to understand we’ve found no unifying diagnosis that we can treat to make him better. But still he says, “Thanks. Thank you for coming and talking with me.” Not “Thank you for fixing my infection with your medicine.” Not “Thank you for figuring out the obscure diagnosis that nobody else could find.” And certainly not “Thank you for curing my cancer.” We have done none of these things. He thanks me for coming into the room. And in these simple words of gratitude, he reminds me of the healing power of care, conversation, explanation, and reassurance. Of why, even when we don’t have the answers, we should still go into the room. I am home putting away dishes later that night when I feel a rush of gratitude for that simple conversation. It hits me suddenly, as I place a clean drinking glass in my cupboard, the gift of those small moments. All those things he could have been—angry, depressed, disengaged, hopeless—he wasn’t. And all those things I could have been—ashamed, helpless, avoidant, exhausted—I left outside the door. Something about our conversaA PIECE OF MY MIND

The Gift of Perspective

Sometimes I wonder why so many bad things happen to me. And then I thank God for the strength to handle it. My Patient SHE IS 41 AND, AFTER MANY CYCLES OF UNSUCCESSFUL in vitro fertilization, finally 18 weeks pregnant, when we get the worrisome news. She is sent to a gastroenterologist by her obstetrician to be evaluated for some rectal bleeding. Sigmoidoscopy shows a 4-cm mass with biopsy confirming adenocarcinoma, stage III at the time of diagnosis. She sees three different oncology teams for opinions, and everyone says the same thing: chemotherapy, radiation, surgery ASAP . . . not wise to carry pregnancy as the cancer may progress to untreatable disease . . . advised to abort. She is not interested in abortion despite the repeated urging of the consultants. She doesn’t want to “let myself down.” This is the child they have worked so hard to have. I am humbled just to watch her digest all of this. She is so small, but so strong. I deeply respect her decision. At the same time I think about her and her family, and I want to start infusing the chemotherapy. I am reviewing her staging CT scan reports and find mention of an incidental splenic artery aneurysm. I am not sure what this means, but soon find out this is a high-risk situation. Many such aneurysms rupture during pregnancy or delivery leading to massive hemorrhage. I wonder how so many things can go wrong at once. Her vascular surgeon recommends urgent coiling for the aneurysm and successfully performs this within days. I wonder if the workup for her rectal cancer has strangely saved her life. After a lot of discussions and recommendations, we all agree on a plan. She will undergo cesarean delivery at 29 weeks and immediately start treatment for her cancer while her daughter is in the NICU. She delivers a baby girl right after Christmas and starts chemotherapy and radiation, which she tolerates poorly while her daughter struggles in the NICU with an infection. She quickly goes for her surgery, during which an enlarged para-aortic lymph node is found adjacent to her duodenum—stage IV. Treatment planning transitions to palliative chemotherapy. Although it makes her sick for several days after each monthly cycle, she continues this. She takes treatment “holidays,” and her disease progresses to involve peritoneal metastases, a brain metastasis, a pneumothorax. Her chemotherapy is restarted. Somewhere along the way her husband loses his job. I’ve stopped counting tragedies because she never does. As her primary care physician for the last three years, I have deeply felt the limits of what I can offer. I can link her to the best oncologists. During times of cancer stability, I can offer her the comfort of clinic visits spent discussing minor ailments, flu vaccines, the basics. And I can be there on the other end of her e-mails and telephone calls, which I am still afraid to answer sometimes . . . afraid to let her down with my limitations one more time. Despite this, she is my most grateful patient. Always remarking on how “lucky” she feels to have such good doctors. She sends me thank-you notes and holiday cards with pictures of her family, and I hang them up. She is grateful that I am present and that is enough. It is not fair. She gives me so much more than this. To me she is a hero. She is mother of the year. She is full of grace and power. I wish I could tell her how grateful I am for what she is showing me, but it would embarrass her. She shrinks from the bright light of my amazement at her strength. Hers is the quiet courage of living each day. Of watching her kids grow and of being there. Of carrying on because “What else can I do?” I rarely see her cry. When she questions why these years have been filled with so many challenges, it is with more wonder than grief. She fights for more than three years, the full extent of her disease often masked by her youth. She dies in the ICU after her lungs quickly fill with tumor. It is hard to let her go, but she made it clear she is not afraid to die. As her strength fades, I can see it ripple through her husband as he makes choices she would have made. Her daughter is 3. Her son is 8. Sometimes I wonder why she had to die so young. Why she had to suffer. Why the bad news kept on coming. Why I couldn’t help her more. And then I thank God for the gift of knowing her.