Publications

OBJECTIVE

To determine whether body weight, body condition score, or various body dimensions were associated with acute thoracolumbar intervertebral disk extrusion or protrusion and whether any of these factors were associated with severity of clinical signs in Dachshunds.

DESIGN

Cross-sectional clinical study.

ANIMALS

75 Dachshunds with (n = 39) or without (36) acute thoracolumbar intervertebral disk extrusion or protrusion.

PROCEDURES

Signalment, various body measurements, body weight, body condition score, and spinal cord injury grade were recorded at the time of initial examination.

RESULTS

Mean T1-S1 distance and median tuber calcaneus-to-patellar tendon (TC-PT) distance were significantly shorter in affected than in unaffected dogs. A 1-cm decrease in T1-S1 distance was associated with a 2.1-times greater odds of being affected, and a 1-cm decrease in TC-PT distance was associated with an 11.1-times greater odds of being affected. Results of multivariable logistic regression also indicated that affected dogs were taller at the withers and had a larger pelvic circumference than unaffected dogs, after adjusting for other body measurements. Results of ordinal logistic regression indicated that longer T1-S1 distance, taller height at the withers, and smaller pelvic circumference were associated with more severe spinal cord injury.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggest that certain body dimensions may be associated with acute thoracolumbar intervertebral disk extrusion or protrusion in Dachshunds and, in affected dogs, with severity of neurologic dysfunction.

NKp30 is a stimulatory receptor on human NK cells implicated in tumor immunity, and is capable of promoting or terminating dendritic cell maturation. To gain a better understanding of NKp30 biology, we have investigated the expression and function of rat NKp30 (rNKp30). We generated stable transfectants of rNKp30 in RNK16 cells, a rat NK lymphoma line, and used a novel panel of mAb against rNKp30 to study this receptor. Using agonistic rNKp30 mAb, we demonstrated that rNKp30 mediates robust IFN-gamma production and cytolytic responses from rNKp30-transfected RNK16 cells. We determined by flow cytometry that rNKp30 is expressed by a subset of primary NK cells isolated from the blood and spleen, and to a lesser extent also on liver NK cells. Stimulation of rNKp30 on primary NK cells led to IFN-gamma production. Liver NK cells expressed low levels of NKp30 and had reduced rNKp30-mediated IFN-gamma responses. During an alloimmune response in vivo, the proportion of the rNKp30(+) NK cell subset in the peripheral blood significantly increased, suggesting that rNKp30 may play an important role during alloactivation. Thus, our data demonstrate that NKp30 is indeed expressed in rodents and is a functional stimulatory receptor in a subset of rat NK cells.

PURPOSE

Resistance to topoisomerase (topo) I inhibitors has been related to down-regulation of nuclear target enzyme, whereas sensitization to topo II inhibitors may result from induction of topo II by topo I inhibitors. Here, we evaluated a sequence-specific administration of a topo I inhibitor followed by a topo II inhibitor.

EXPERIMENTAL DESIGN

Twenty-five patients with advanced or metastatic malignancies were treated with increasing doses (0.75, 1.0, 1.25, 1.5, 1.75, or 2.0 mg/m(2)) of 9-nitrocamptothecin (9-NC) on days 1 to 3, followed by etoposide (100 or 150 mg/d) on days 4 and 5. At the maximally tolerated dose, 20 additional patients were enrolled. The median age was 60 years (range, 40-84 years). Endpoints included pharmacokinetic analyses of 9-NC and etoposide, and treatment-induced modulations of topo I and II expression in peripheral blood mononuclear cells.

RESULTS

Neutropenia, thrombocytopenia, nausea, vomiting, diarrhea, and fatigue were dose-limiting toxicities and occurred in six patients. Despite a median number of four prior regimens (range 1-12), 2 (4%) patients had an objective response and 13 (29%) patients had stable disease. In contrast to the expected modulation in topo I and IIalpha levels, we observed a decrease in topo IIalpha levels, whereas topo I levels were not significantly altered by 9-NC treatment.

CONCLUSIONS

Sequence-specific administration of 9-NC and etoposide is tolerable and active. However, peripheral blood mononuclear cells may not be a predictive biological surrogate for drug-induced modulation of topo levels in tumor tissues and should be further explored in larger studies.

PURPOSE

In phase I studies with oral CI-1033, dose-limiting toxicities were primarily gastrointestinal, supporting the exploration of i.v. dosing to achieve optimal drug exposures by increasing bioavailability.

EXPERIMENTAL DESIGN

Fifty-three patients with advanced nonhematologic malignancies received i.v. CI-1033 via 30-minute infusions (10-500 mg) on a thrice-weekly schedule. Pharmacokinetic samples were collected on days 1 and 8 and evaluated using noncompartmental analysis.

RESULTS

Dose levels evaluated were 10, 20, 30, 45, 67.5, 100, 150, 225, 337.5, and 500 mg. The maximum administered dose was 500 mg, whereas the maximum tolerated dose was 225 mg. The most common treatment-related grade 1 to 2 adverse events were rashes (38% of patients), nausea (17%), vomiting (17%), stomatitis (14%), and diarrhea (13%). Most common grade 3 adverse events were hypersensitivity reactions (7.5%), rashes (3.8%), and diarrhea (3.8%). No grade 4 toxicities were observed. Ten of the 53 (19%) patients had disease stabilization at their first efficacy evaluation visit (including two with minor responses). A 5- to 10-fold increase in i.v. C(max) was noted with a 3-fold increase in AUC compared with oral CI-1033 at equivalent doses. Treatment-related gastrointestinal adverse events were notably less frequent with this i.v. regimen.

CONCLUSIONS

CI-1033 was safely given i.v. up to 225 mg/dose on a thrice-weekly schedule, with evidence of antitumor activity. At equivalent doses, the bioavailability of i.v. CI-1033 is thrice that of the oral formulation. Treatment with i.v. CI-1033 is feasible and may be warranted when increased drug exposures are desired.

BACKGROUND

Little is known about patient characteristics associated with comprehension of consent information, and whether modifications to the consent process can promote understanding.

OBJECTIVE

To describe a modified research consent process, and determine whether literacy and demographic characteristics are associated with understanding consent information.

DESIGN

Descriptive study of a modified consent process: consent form (written at a sixth-grade level) read to participants, combined with 7 comprehension questions and targeted education, repeated until comprehension achieved (teach-to-goal).

PARTICIPANTS

Two hundred and four ethnically diverse subjects, aged > or = 50, consenting for a trial to improve the forms used for advance directives.

MEASUREMENTS

Number of passes through the consent process required to achieve complete comprehension. Literacy assessed in English and Spanish with the Short Form Test of Functional Health Literacy in Adults (scores 0 to 36).

RESULTS

Participants had a mean age of 61 years and 40% had limited literacy (s-TOHFLA<23). Only 28% of subjects answered all comprehension questions correctly on the first pass. After adjustment, lower literacy (P=.04) and being black (P=.03) were associated with requiring more passes through the consent process. Not speaking English as a primary language was associated with requiring more passes through the consent process in bivariate analyses (P<.01), but not in multivariable analyses (P>.05). After the second pass, most subjects (80%) answered all questions correctly. With a teach-to-goal strategy, 98% of participants who engaged in the consent process achieved complete comprehension.

CONCLUSIONS

Lower literacy and minority status are important determinants of understanding consent information. Using a modified consent process, little additional education was required to achieve complete comprehension, regardless of literacy or language barriers.

BACKGROUND

While limited literacy is common and its prevalence increases with age, no prospective study has assessed whether limited literacy is associated with mortality in older adults.

OBJECTIVE

To assess the association of limited literacy with mortality.

DESIGN AND SETTING

Five-year prospective study from 1999 to 2004 of community-dwelling elders from Memphis, TN, and Pittsburgh, PA, who were from the Health, Aging, and Body Composition study. Subjects' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into limited (0 to 8th grade reading level) or adequate literacy (> or = 9th grade reading level).

PARTICIPANTS

Two thousand five hundred and twelve black and white elders without baseline functional difficulties or dementia.

MEASUREMENTS

Time to death.

RESULTS

Participants' mean age was 75.6 years, 48% were male, 38% were black, and 24% had limited literacy; the median follow-up time was 4.2 years. Compared with those with adequate literacy, those with limited literacy had a higher risk of death (19.7% vs 10.6%) with a hazard ratio (HR) of 2.03 (95% confidence intervals [CI], 1.62 to 2.55). After adjusting for demographics and socioeconomic status, co-morbid conditions, self-rated health status, health-related behaviors, health care access measures, and psychosocial status, limited literacy remained independently associated with mortality (HR 1.75; 95% CI, 1.27 to 2.41).

CONCLUSIONS

Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly. Given the growth of the aging population and the prevalence of chronic diseases, the mechanisms by which limited literacy is associated with mortality in the elderly warrant further investigation.

OBJECTIVES

To describe patterns of home health and hospice use by older cancer patients and a comparison group of older persons without cancer. To identify predictors of home care and hospice utilization.

DESIGN

Retrospective analysis using the Surveillance, Epidemiology and End Results (SEER)-Medicare Database, a linkage of the SEER Program of the National Cancer Institute (an epidemiological surveillance system of population-based tumor registries) and Medicare Claims.

SETTING

The SEER data used in this paper cover a service area that includes approximately 14% of the U.S. population, including the states of Connecticut, Hawaii, Iowa, and New Mexico and the metropolitan areas of Detroit, San Francisco-Oakland, Atlanta, Seattle-Puget Sound, Los Angeles County, and San Jose-Monterey.

PARTICIPANTS

Five analytical samples were drawn. The first consisted of all cases with a diagnosis of cancer in 1997 to 1999 who were eligible for services in calendar year 1999 (n=120,072). The second and third were subsamples of these and consisted of cases with a new cancer diagnosis in 1999 (n=46,373) and cases who died in 1999 (n=41,483). The fourth consisted of a comparison sample without cancer (n=160,707). The fifth was a subsample of this and consisted of those who died in 1999 (n=6,639).

MEASUREMENTS

Utilization rates of home health and hospice services.

RESULTS

Twenty-nine percent of cancer patients used home health services, and 10.7% used hospice services, compared with 7.8% of noncancer patients who used home health and less than 1% who used hospice. Half (51.4%) of cancer patients who used home health did not have cancer listed as an admitting diagnosis for the use of those services. Home health utilization was lowest for unmarried men.

CONCLUSION

This is the first study to evaluate community-based home health and hospice utilization by older cancer patients. Future studies must begin to address what constitutes appropriate utilization.

INTRODUCTION

Most medical schools are remiss in preparing physicians in end-of-life communication skills. As a result, many residents are uncomfortable with approaching the patient, have not developed the skills required to discuss the patients' wishes, and avoid end-of-life conversations.

OBJECTIVE

To evaluate an educational intervention focused on teaching residents skills to discuss advance directives.

METHODS

Medicine Residents attended a morning report consisting of both didactic training and participation in a role-play exercise. Charts of inpatients were audited ten days prior to and five days subsequent to the intervention to ascertain if there was a documented do-not-resuscitate (DNR) discussion.

RESULTS

Seventy-nine records of patients assigned to eight physicians who attended the intervention and who were responsible for patients before and after the intervention were reviewed. Of the patients assigned to these residents before the intervention, 32% had a documented DNR discussion. Thirty-four (34%) of the physicians had discussions after the intervention, demonstrating only minimal improvement.

CONCLUSIONS

A single intervention may be inadequate to affect physician practices related to DNR discussions. Physicians may need more interactive, experiential learning opportunities and related supervision over the course of their training in order to improve these communication skills. A chart review that only records if a DNR discussion was documented in the medical record may not be the best tool to evaluate the success of this educational intervention. Improvement in attitudes and knowledge were not able to be measured.

OBJECTIVE

To examine the association of heart disease with depression and the impact of treatment with anti-depressants on this association in older males with type 2 diabetes.

RESEARCH DESIGN AND METHODS

In this cross-sectional study, data were collected from the electronic medical record system of the Veterans Affairs Medical Center (VAMC) in a large mid-western city in the United States. Subjects were 8185 males older than 40, with a history of type 2 diabetes, who had visited the VAMC within the previous 6 years. Odds ratios were used to measure bivariate associations; multivariate logistic regression was used to adjust for potential confounding factors.

RESULTS

After adjustments for confounding variables, significant associations were found between depression and any adverse heart event (OR=1.34, p=0.001), coronary artery disease (OR=1.23, p=0.039), myocardial infarction (MI; OR=1.77, p<0.001), and angioplasty (OR=1.36, p=0.034). Examination of the interaction between depression and anti-depressant prescription status indicated that, except for MI, these associations were no longer significant among those who had been prescribed anti-depressants, but remained significant and were increased in magnitude among those who had not been prescribed anti-depressants.

CONCLUSIONS

These findings support the premise that co-morbid depression in diabetics is associated with the occurrence of adverse heart events, and further suggest that treatment of depression with anti-depressants moderates this association.