Faculty Bibliography

Donepezil (Aricept) is a cholinesterase inhibitor approved for the treatment of Alzheimer's disease. Immediate release formulations of 5- and 10-mg tablets were approved by the Food and Drug Administration in the United States in 1996. In July 2010, the Food and Drug Administration approved a 23-mg sustained release (SR) formulation. The SR formulation may provide additional benefit to patients receiving 10 mg daily but the incidence of adverse reactions is increased. We derived plasma concentration profiles for higher dose immediate-release formulations (15 mg once daily, 10 mg twice daily, and 20 mg once daily) and for the profile anticipated to result from the 23-mg SR formulation. Our model predicts similar steady-state concentration profiles for 10 mg twice daily, 20 mg once daily, and 23 mg SR once daily. This provides the theoretical basis for incremental immediate release dose escalation to minimize the emergence of adverse reactions and the potential to offer a cost-effective alternative to the SR formulation with currently approved generic immediate release formulations.

BACKGROUND:Cholinesterase inhibitors are indicated for the treatment of Alzheimer-type dementia. There are few direct comparative studies of adverse effects or studies to suggest clinical superiority of one inhibitor over the others. OBJECTIVE:The objective of this study was to relate pharmacokinetic differences among the agents to potential clinical considerations. METHODS:Population pharmacokinetics were obtained from US Food and Drug Administration-approved label information and published literature. Plasma concentration-time profiles were derived from these parameters using noncompartmental pharmacokinetic modeling. RESULTS:Plasma concentration profiles differed significantly among different agents and between different formulations of the same agent. CONCLUSIONS:The initial choice among the various cholinesterase inhibitors requires consideration to adherence and cost. Consideration to differences in pharmacokinetics among these drugs provides a better understanding for the clinical practice of dose titration, identification and management of drug-related side effects, and lapses in therapy. Pharmacokinetic considerations among the various agents and formulations provide the clinician with options to enhance therapy when these agents are chosen for treatment of patients with Alzheimer-type dementia.

OBJECTIVES/OBJECTIVE:Internal medicine residents often provide hospital care for patients who are admitted from and discharged to nursing homes. This pilot study surveyed internal medicine residents for their assumptions and perceptions about demographics and regulations in the nursing home setting. DESIGN/SETTING/PARTICIPANTS/METHODS:Internal medicine residents at Winthrop University Hospital in Long Island, New York, were asked to participate in this anonymous, voluntary, and self-administered written survey during October 2006. MEASUREMENTS/METHODS:Survey answers were collected and analyzed using SAS 9.1 (SAS Institute, Inc., Cary, NC). RESULTS:The mean responses were very close to the actual data; however, the range and standard deviations (SD) of responses revealed a wide variation in perceptions about nursing home demographics and regulations. For example, the internal medicine residents estimated that 60% of nursing home beds are for long-term care but the responses ranged from 20% to 90%, with an SD of 21. Awareness about regulations such as payment sources and the role of the medical director was poor. Fifty-two percent of respondents stated that Medicare is the primary source of payment for long-term care. Eighty-five percent of the respondents believed that the medical director of a nursing home could be a physician, nurse, social worker, or nursing home administrator. CONCLUSION/CONCLUSIONS:Although internal medicine residents have high exposure to nursing home patients, many of those surveyed have incorrect perceptions about nursing home demographics and requirements. Further research is required to demonstrate the impact of formal geriatric medicine education on internal medicine residents' knowledge regarding nursing home demographics and regulations.

OBJECTIVE:To compare diurnal body temperature between young and old subjects. DESIGN/METHODS:Analysis of oral temperatures obtained from 167 elderly subjects residing in the nursing home and 21 high school students. SETTING/METHODS:Two nursing homes and a high school. PARTICIPANTS/METHODS:Participants were 167 nursing home subjects and 21 high school students. MEASUREMENTS/METHODS:Oral temperatures were measured in the morning and afternoon among nursing home subjects and high school students using an electronic digital thermometer. RESULTS:The average age of old and young subjects was 82.5 and 14.6 years, respectively. Mean morning temperature was not different between the old (97.3 +/- 0.82 degrees F) and young (97.1 +/- 1.03 degrees F). In young subjects, afternoon temperatures increased by 0.69 +/- 1.15 degrees F to 97.8 +/- 0.92 degrees F (P < .05) while temperatures in old subjects rose by 0.14 +/- 1.11 degrees F to 97.4 +/- 0.93 degrees F (P > .05). The increase during the day was greater for young subjects compared with the old (P < .04). Two of 20 young and 8 of 167 old subjects had temperatures of 98.6 degrees F or greater in the morning while 3 of 20 young and 21 of 163 old subjects achieved this temperature or higher in the afternoon. CONCLUSION/CONCLUSIONS:Both older and young subjects have mean oral body temperatures lower than 98.6 degrees F. Relatively few young and old subjects even achieve this temperature. The diurnal rise in body temperature was less among nursing home subjects compared with younger subjects.

A 67-year-old woman with diabetes mellitus, chronic renal insufficiency, and recurrent urinary tract infections experienced encephalopathy and myoclonus while receiving cefepime. The adverse drug event was accompanied by elevated cefepime levels and abnormal electroencephalograms. This syndrome resolved after discontinuation of cefepime. Neurotoxicity is a known but possibly underreported adverse event associated with cefepime in patients with renal impairment who receive relatively excessive doses. Most cases reverse on drug cessation. In patients with renal disease, the maintenance dosage should be reduced and the patient monitored for neurotoxicity. Cefepime toxicity should be suspected whenever a patient receiving the drug experiences a change in mental status or myoclonus.

OBJECTIVES/OBJECTIVE:To ascertain body temperatures in older people. DESIGN/METHODS:Analysis of oral temperatures obtained from elderly subjects residing in the community and nursing home. SETTING/METHODS:A single nursing home, office setting, and community center. PARTICIPANTS/METHODS:One hundred nursing home residents and 50 subjects residing in the community. MEASUREMENTS/METHODS:Three oral temperatures were measured in nursing home residents and once in community dwellers using an electronic digital thermometer. RESULTS:The average age of subjects was 80.7. Temperatures ranged from 94.0 degrees F to 99.6 degrees F. In nursing home subjects, the 6 a.m. mean temperature was 97.3 degrees F, 4 p.m. mean was 97.4 degrees F, and 10 p.m. mean was 97.8 degrees F. The single midday mean temperature in community dwellers was 97.7 degrees F. Ninety-seven of 100 (97%), 94 of 100 (94%), and 83 of 96 (86%) recordings were below 98.6 degrees F in nursing home residents at 6 a.m., 4 p.m., and 10 p.m., respectively. Similarly, 45 of 50 (90%) community dwellers had midday temperatures below 98.6 degrees F. Repeated-measures analysis demonstrated an increase in temperature during the day. The increase was greatest in the youngest old, with no significant change in body temperature over the course of the day in the oldest old. CONCLUSION/CONCLUSIONS:Older subjects have mean oral body temperatures lower than 98.6 degrees F. Relatively few even achieve this temperature. In nursing home residents, the oldest were coldest and failed to demonstrate a diurnal rise in body temperature.