A nurse, a pharmacist, a hospital administrator and an oncologist were all in line at the bank when a robber burst in waving a machine gun. Soon, police sirens were heard in the distance and the bank robber took all four as hostages. He crammed them into his small car and raced away. The police were soon gaining on them, and he turned to the pharmacist and said, “Give me one good reason why I shouldn’t throw you out of the car!”
“Uh, electronic medication dispensing, local flu shots, Zoster vaccines…”
“Those are stupid reasons!” the robber said, and threw him from the car. But the police were still gaining, and soon the robber turned to the administrator and said, “Give me one good reason why I shouldn’t throw you from the car!”
“Ach, EPIC electronic medical records, satellite ERs, flexible ICU beds…”
“Those are stupid reasons!” the robber yelled, and threw him from the car. But the police were still gaining, and moments later the robber turned to the oncologist and shouted, “Give me one good reason why I shouldn’t throw you from the car!”
The oncologist gathered herself and was about to begin when the nurse raised his hand, and said, “Can you throw me from the car first? I don’t think I can stand another speech on the importance of molecular medicine in oncology!”
Since the discovery of gene cloning and DNA sequencing three decades ago, the National Institutes of Health has spent billions on research into the molecular defects behind diseases. I should know, I have received several million myself. For many decades there was no reward for all this money spent. Physicians kept talking about the importance of understanding the molecular defects that cause disease, but there were few new treatments discovered that came from that research. Many politicians were like the nurse above, “Throw me from the car first, because I cannot stand to hear any more about how important all this molecular research is to medicine!”
I spend several days every year lobbying Congress on behalf of funding medical research, especially at the NIH. The politicians and their staffers roll their eyes when I come around, listen patiently, then breathe a sigh of relief when I am gone.
But things have changed. This issue of The SCOPE highlights several new treatments that have come from understanding the molecular biology behind disease. These treatments would not have been possible if the fundamental structural alterations at the amino acid level were not well-defined. One such novel treatment is the drug ibrutinib, which irreversibly inhibits proliferation signaling, in low grade lymphoid neoplasia. Another is ivakaftor, which straightens out the cystic fibrosis transmembrane conductance receptor, so that it can better transport sodium in some cases of cystic fibrosis.
Neither of these drugs would have been discovered if it were not for the molecular understanding of these two diseases. There is a lesson in all this: Investment in medical research works, but it takes time, and pulling the plug too soon harms patients.
Cystic fibrosis (CF) is the most common life-shortening, multi-organ system disease affecting Caucasians today. The CF transmembrane conductance regulator (CFTR) protein regulates ion transport across the apical surface of epithelial cells found throughout the respiratory tract, intestines and skin. A gene mutation resulting in the absence or dysfunction of the CFTR protein results in dry, thickened mucus that inhibits normal mucociliary clearance. This predisposes patients to not only develop chronic to chronic airway inflammation and destruction but also to pancreatic autolysis, leading to chronic respiratory failure, as well as malnutrition, osteoporosis and CF related diabetes.
Advancements, including early diagnosis, increased therapeutic options targeting infection and the inflammatory process, novel airway clearance techniques, and improved nutritional status, have resulted in improved survival. Currently, registry data indicates median survival age in Europe and North America is roughly 35 years and patients born today are expected to have a median survival into their 60s.
In the last five years, research efforts have yielded new therapeutic options, including compounds specifically targeting the CFTR protein. Ivacaftor (Kalydeco®) is the first medication in the market to affect the CFTR. It works as a potentiator of CFTR in mutations where CFTR is in the right position but the gate of the channel doesn’t work. Clinical trials using Ivacaftor showed a significant improvement in lung function, decreased infections, increased weight, improvement in quality of life and improvement in hemoglobin A1c.
The adult CF center at UF Health has participated in trials using a combination of Ivacaftor and CFTR correctors (VX-809®) (VX-661®) in an attempt to target the most common mutation, Delta F508. UF continues to participate in new research efforts, working not only to improve health outcomes in patients with CF but also to cure the disease. Current projects include new ways to diagnose airway inflammation and infections in a noninvasive way and exploration at a molecular level a novel way to deliver gene therapy to airway cells.
FOR MORE INFORMATION, PLEASE VISIT PULMONARY.MEDICINE.UFL.EDU. TO REFER A PATIENT, PLEASE CALL 352.274.8740 OR 888.254.7586, OR EMAIL CFCENTER@MEDICINE.UFL.EDU.
Fibromyalgia (FM), one of the most common “rheumatic” disorders in the general population, is an illness characterized by abnormally enhanced pain processing of peripheral tissue signals (hyperalgesia or allodynia), which can amplify minor discomforts into majorpain experiences.
Psychological, behavioral and social factors can contribute to FM and are relevant for its treatment. Psychiatric vulnerabilities, including anxiety, depression, obsessive-compulsive and post-traumatic stress disorders, are a significant risk factor, which is relevant as neurotransmitters mediating pain processing may also affect mood, fatigue, memory and sleep. Additional risk factors for developing FM include traumatic events, insomnia, obesity, sedentary lifestyle and poor coping skills. On one hand, maladaptive factors such as catastrophizing and fear of movement may worsen pain and function; on the other hand, such psychological contributions are readily treatable with cognitive behavioral therapy. Overall, non-pharmacological interventions for FM include simple strategies like stress reduction, improved sleep hygiene and increased physical activity. These interventions represent the basis for rational FM therapy and should always be emphasized as an important adjunct to pharmacological therapy.
Pharmacological treatments of FM have made significant progress with the introduction of several FDA-approved medications. These treatments include serotonin-norepinephrine reuptake inhibitors (duloxetine and milnacipran) and anti-convulsants (pregabalin). Because single use of these medications has shown only moderate effectiveness for FM pain and dysfunction, most patients will require more than one analgesic drug. Furthermore, frequently present comorbidities like anxiety and depression may also require additional medications. Trigger point injections, nerve blocks, TENS units and topical therapies are often helpful treatments as they directly affect relevant pain generators. Opioids have generally not been effective for most chronic pain disorders, including FM.
Overall, rational management of FM frequently requires integration of nonpharmacological and pharmacological treatments while simultaneously empowering patients to become active participants in their own care. FM is most often diagnosed and treated in the primary care setting, whereas referrals to specialists are only required for patients with complex presentations or for patients whose symptoms are not responding to therapy. Whenever feasible, treatment should be provided by multidisciplinary teams, including physical and occupational therapists, as well as providers experienced in cognitive behavioral therapy.
The UF Division of Rheumatology and Clinical Immunology has an ongoing NIH-supported research program on mechanisms of chronic musculoskeletal pain and fatigue, as well as an active fibromyalgia clinic, led by Roland Staud, MD.
FOR MORE INFORMATION OR TO REFER A PATIENT, PLEASE CALL US AT 352.265.8901 OR EMAIL PAINRESEARCH@MEDICINE.UFL.EDU.
A PHONE RINGS IN THE UF HEALTH SHANDS DEPARTMENT OF INFECTION CONTROL:
“This is Infection Control. How may I help you?”
A NURSE FROM A GENERAL MEDICINE UNIT:
“We’ve had a chronic obstructive pulmonary disease patient in a double room on our floor for 10 days, and she was coughing a lot. A sputum sample is now growing acid-fast bacilli suspicious for tuberculosis. Our patient was never on isolation, has had three other roommates since admission, and none of the staff or physicians caring for her have worn masks. What do we do now?”
This is the sort of call that the infection control team at UF Health fields every day. Our dedicated practitioners are experts in dealing with potential crises such as these and provide a reliable resource to the patient care areas they serve. Each has expertise in particular areas relevant to infection control, including OR policies and procedures, sterile processing of equipment and data management.
Equally important is rapid response to possible emergencies and prevention. Our mission is to promote patient safety by reducing the risk of acquiring and transmitting infections, and to be a recognized leader in health care epidemiology and infection control. This is an enormous task, and to fulfill it, the team must constantly engage colleagues throughout UF Health and beyond, including the clinical quality and patient safety office, environmental health and safety, the department of health, the antimicrobial management team and the clinical microbiology laboratory.
Last year, one of our key efforts was the control of multidrug-resistant organisms. This required a multifaceted approach, the most conspicuous of which was the renovation of our UF Health Burn Intensive Care Unit. The state-of-the-art unit was designed with input from the infection control team and represents the best in unit design from an infection control perspective.
But no amount of design can substitute for the personal responsibility we all bear for keeping our patients and each other safe from transmissible infections by practicing hand hygiene, reading the personal protective equipment requirements on isolation signs and getting vaccinated for influenza. You are the first line of defense against disease transmission. Infection control is everyone’s job!
IF YOU HAVE AN INFECTION CONTROL QUESTION OR CONCERN, PLEASE CALL US AT 352.265.0BUG (0284).
BRENTUXIMAB VEDOTIN (ADCETRIS®)
An immunotoxin used to treat CD30+ lymphomas, brentuximab vedotin (Adcetris®) is the first CD30-directed antibody-drug conjugate and was granted accelerated approval by the U.S. Food and Drug Administration. It has been approved for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplantation or after failure of two prior multi-agent chemotherapy regimens in those patients who are not transplant candidates.
In a single-arm phase II trial of 102 patients, overall response rates were 73%, with a complete response rate of 32%. The drug was also approved for use in patients with relapsed systemic anaplastic large cell lymphoma, or ALCL.
A phase II trial with 52 relapsed ALCL patients yielded single-agent response rates of 86% and a complete response rate of 57%.
Another target for novel lymphoma therapies is the Bruton’s tyrosine kinase (BTK), an enzyme that promotes growth of a variety of B-cell malignancies, including chronic lymphocytic lymphoma (CLL), mantle cell lymphoma (MCL) and others. In MCL, a single-agent treatment with the oral BTK-inhibitor, ibrutinib (Imbruvica™), was approved by the FDA after showing strong response rates in heavily pretreated patients.
In a phase II trial, 111 of recurrent or refractory mantle cell lymphoma patients, the overall response rate was 68%, with a 17% complete response rate. Oral ibrutinib has also shown single-agent activity in recurrent, previously treated CLL. A study of 85 patients with relapsed or refractory CLL patients yielded an overall response rate of 71%, though only 2% complete responses.
“For many of these patients, there are few good treatment options remaining. These therapies are providing hope.” — Merry-Jennifer Markham, MD, Assistant Professor Professor in the Division of Hematology-Oncology
OUR TEAM OF LYMPHOMA SPECIALISTS – MERRY-JENNIFER MARKHAM, MD, JAMES LYNCH, MD, AND NAM DANG, MD. FOR MORE INFORMATION OR TO REFER A PATIENT, PLEASE CALL 352.265.0725.