Cancer drug dosing in kids, medication-related delirium, and battery swallowing take top honors at seminar

Studies of cancer drug dosing in children, possible medication links to delirium in hospital patients, and how to decide when swallowed batteries may call for invasive removal took top honors at the Department of Clinical Pharmacy’s 14th annual Spring Research Seminar.

The poster session, covering a total of 71 projects, highlighted research by UCSF School of Pharmacy student pharmacists, residents, and faculty members, was held on May 1, 2012 on the Parnassus Campus.

Rifkind Award Winners

Winners of the 5th annual Gary Rifkind Spring Research Seminar Awards are:

Student pharmacist

Caroline Lindsay, PharmD (class of 2012) for the poster: “Medications Associated with the Development of Delirium in Hospitalized Patients.”

Resident

Elisabeth Birdsall, PharmD, for the poster: “Characteristics of Cylindrical Battery Ingestion — An 11-Year Retrospective Review of Cases Reported to a Poison Control Center.”

Junior Faculty

Janel Long-Boyle, PharmD, PhD, for the poster: “An Interim Evaluation of Systemic F-ara-a Exposure in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients Using an Optimal Sampling Design.”

The Rifkind awards, $1,000 each, were created to recognize and celebrate clinical pharmacy research. They are the gift of Gary Rifkind, PharmD, a UCSF School of Pharmacy alumnus, Class of 1960.

Are medications risk factors for delirium in hospital patients?

Lindsay et al.’s poster cited studies demonstrating that delirium in hospital patients—a state of confused thinking often accompanied by incoherent speech, agitation, and even hallucination—leads to increases in length of stay, severity of illness, and mortality.

Her study examined the association between medications and the development of delirium in more than 200 consecutive patients admitted from the emergency department of UCSF Medical Center to non-intensive-care medicine, cardiology, neurology, and neurovascular hospital wards.

Patients in the study were assessed upon admission for their cognitive (i.e., mental) status then followed for up to six days to detect if they developed delirium. This information was compared with records of the medications administered during their hospitalization.

Results and conclusions: Twenty-five of the patients (12 percent) developed delirium. When multiple variables were taken into account, Lindsay’s study found that the key risk factors for those patients were:

• receiving five or more new regularly scheduled medications.
• impaired mental state at the time of hospital admission.

Lindsay was careful to note that many interacting factors contribute to delirium and the study’s limited patient sample could not provide definitive answers. Her work suggests further exploration is needed on whether particular drugs contribute to delirium, especially in elderly patients with pre-existing cognitive impairment.

Swallowed batteries: Which patients may need invasive removal?

The study by Birdsall et al. was a collaboration with the four-center California Poison Control System, which is administered by the UCSF School of Pharmacy. It reviewed 131 cases of cylindrical battery ingestion reported to the system between 2000 and 2010 that were confirmed by x-rays, passage out of the body, or medical retrieval.

Such battery ingestion can have serious consequences including permanent injury or even death. In this review, three patients developed gastrointestinal (GI) perforations, and one died.

As there are no standard treatment guidelines for such ingestion cases, a “watch and wait” approach is most common. The goal of the study was to identify risk factors for patients who require invasive removal of the batteries.

Nearly three of four ingestions were related to a psychiatric disorder. In two-thirds of the cases, which involved patients aged 3 months to 63 years, the battery size ingested was AA. Twenty-four percent of the patients underwent invasive removal, predominantly via endoscopy (a tube down the throat), but also via surgery.

Conclusions: Patients who were most likely to require invasive removal were those who had:

• abdominal pain.
• ingested multiple batteries.
• previous surgical removal of ingested foreign bodies. (Abdominal surgery leaves scar tissue in the GI tract where batteries are more likely to lodge and cause damage.)

Determining dosing of a cancer treatment drug in children

Boyle’s et al. study is the first to examine the proper dosing for children of fludarabine, a drug used to enhance the uptake of transplanted stem cells to treat cancers of the blood or bone marrow, such as leukemia.

The goal of this interim project (part of a larger study taking place over three years) was to ensure that the selected schedule of blood sample collections was adequate to analyze the drug’s pharmacokinetics and pharmacodynamics (PK-PD)—that is, the rates at which the drug is absorbed, distributed, metabolized and excreted as well as its effects relative to a particular size dose—in children under age 17.

Conclusions: The study found that the sampling schedule being used allowed for accurate estimations of important drug concentrations in the blood and measures of clearance.

The interim study’s analysis of the first 16 patients found that children who weighed less than 22 pounds cleared fludarabine from the body more slowly. This suggests that body weight may be used to predict the drug’s clearance and that lower doses may be required in very small children to prevent over-exposure.

This PK-PD study will continue to enroll patients over the next two years to confirm these interim pharmacokinetic findings. It will also measure responses to dose levels to help determine the most safe and effective fludarabine regimens for children.