Publications

BACKGROUND

A number of agents, including aspirin, nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, folic acid, calcium, and vitamins, have been evaluated for their potential in chemoprevention of sporadic colorectal adenomas or cancer. Preclinical data suggest that 5-aminosalicylates also may have a chemopreventive effect.

AIM

To investigate chemoprevention of colonic polyps with balsalazide, a 5-aminosalicylate prodrug.

METHODS

In this randomized, double-blind, placebo-controlled study, adults diagnosed with small polyps in the rectosigmoid colon were treated with either balsalazide 3 g/d or placebo for 6 months. Follow-up lower endoscopy was performed, and all polyps were measured and analyzed histologically. The primary endpoint was reduction in mean size of the largest polyp per subject.

RESULTS

Among 241 participants screened, 86 were randomized to treatment, with 75 subjects evaluable. Balsalazide 3 g/d (n = 38) did not significantly reduce the mean size of the largest colonic polyp or the number of polyps compared with placebo (n = 37). Although not significant, post-hoc analysis revealed that total adenoma burden per subject, calculated as the sum of the volumes of all adenomas in mm3, increased by 55% in the balsalazide group compared with 95% in the placebo group.

CONCLUSIONS

Although balsalazide did not have significant chemopreventive effects on established colonic polyps, these results can aid in designing future prospective studies.

PURPOSE

Resources for studying inflammatory bowel disease (IBD) are needed in evaluations of drug safety including traditional drugs and new biologics agents. We developed an IBD registry, with ascertainment from computerized visit information.

OBJECTIVE

We sought to characterize the positive predictive value (PPV) of IBD case-finding using computerized data compared with chart review.

METHODS

We identified 2906 persons aged 89 years or younger with one or more IBD diagnoses in computerized visit data during the period of 1996-2002. The diagnosis of IBD was confirmed through chart review. Adopting chart review as the gold standard, the validity of computerized encounter data to determine IBD was estimated.

RESULTS

Among the 2906 study subjects with one or more ICD-9 diagnosis codes of 555 or 556 in computerized data, 81% were confirmed as having IBD by chart review. Defining cases as those who underwent two or more visits without regard to diagnostic procedures or drug utilization maximized the correct classification of cases (PPV, 95%).

CONCLUSIONS

The quality of IBD diagnoses in computerized data is adequate to meet the aims of a wide range of research studies.

OBJECTIVE

Determine the relationship between traumatic brain injury (TBI) and premature mortality and intracranial neoplasms occurring 6 months or more after TBI.

PARTICIPANTS

Not applicable.

DESIGN

Systematic review of the published, peer-reviewed literature.

PRIMARY MEASURES

Not applicable.

RESULTS

We identified 23 studies that examined premature mortality following TBI and 16 that addressed intracranial neoplasms. There was clear evidence of an association between penetrating brain injury and premature mortality among patients surviving at least 6 months; and similarly compelling evidence of an association between moderate or severe TBI and premature mortality among patients injured severely enough to require acute rehabilitation. There was inadequate evidence to reach a conclusion about whether other closed head injuries were associated with premature mortality. For intracranial neoplasms, there was an apparent association between TBI and intracranial neoplasms diagnosed within 1 year following TBI; however, these tumors were likely incidentally found during evaluation for the TBI. For tumors diagnosed more than 1 year post injury, the evidence was inadequate to conclude that there was an association, although at least 1 very large registry-based study found a borderline association.

CONCLUSION

More severe TBI (ie, penetrating and moderate and severe TBI requiring rehabilitation) is associated with premature mortality among patients surviving at least 6 months. There is no clear evidence for an association between TBI and intracranial neoplasms presenting more than 1 year following TBI.

BACKGROUND

Food insecurity is increasingly recognized as a barrier to optimal treatment outcomes, but there is little data on this issue. We assessed associations between food insecurity and mortality among HIV-infected antiretroviral therapy-treated individuals in Vancouver, British Columbia, and whether body max index (BMI) modified associations.

METHODS

Individuals were recruited from the British Columbia HIV/AIDS drug treatment program in 1998 and 1999 and were followed until June 2007 for outcomes. Food insecurity was measured with the Radimer/Cornell questionnaire. Cox proportional hazard models were used to determine associations between food insecurity, BMI, and nonaccidental deaths when controlling for confounders.

RESULTS

Among 1119 participants, 536 (48%) were categorized as food insecure and 160 (14%) were categorized as underweight (BMI < 18.5). After a median follow-up time of 8.2 years, 153 individuals (14%) had died from nonaccidental deaths. After controlling for adherence, CD4 counts, and socioeconomic variables, people who were food insecure and underweight were nearly 2 times more likely to die (adjusted hazard ratio = 1.94, 95% confidence interval = 1.10 to 3.40) compared with people who were not food insecure or underweight. There was also a trend toward increased risk of mortality among people who were food insecure and not underweight (adjusted hazard ratio = 1.40, 95% confidence interval = 0.91 to 2.05). In contrast, people who were underweight but food secure were not more likely to die.

CONCLUSIONS

Food insecurity is a risk factor for mortality among antiretroviral therapy-treated individuals in British Columbia, particularly among individuals who are underweight. Innovative approaches to address food insecurity should be incorporated into HIV treatment programs.

Food insecurity and HIV/AIDS are intertwined in a vicious cycle that heightens vulnerability to, and worsens the severity of, each condition. We review current knowledge and research priorities regarding the impact of food insecurity on HIV transmission risk and clinical outcomes. Observational studies suggest that food insecurity is associated with increased HIV transmission risk behaviors and decreased access to HIV treatment and care. Among individuals receiving antiretroviral therapy (ART), food insecurity is associated with decreased ART adherence, reduced baseline CD4 cell count, incomplete virologic suppression, and decreased survival. Integration of food security interventions into HIV/AIDS treatment programs is essential to curtail the HIV/AIDS epidemic and improve health and quality of life among those infected. Longitudinal research applying validated measurement tools is needed to better understand the mechanisms through which food insecurity adversely impacts HIV transmission, treatment, and care. Research should compare the effectiveness of various food assistance and livelihood strategies.

Two decades ago the importance of transporter-enzyme interplay and its effects on drug bioavailability and hepatic disposition were first recognized. Here we review the history of uncovering and defining this interplay with a primary emphasis on studies from our laboratory. We review the early 1990s oral bioavailability studies that found that the highly lipophilic, poorly water-soluble cyclosporine formulation on the market at that time did not have an absorption problem, but rather a gut metabolism problem. This led to studies of the interactive nature of CYP3A and P-glycoprotein in the intestine, and investigations of this interplay using cellular systems and isolated perfused rat organ studies. Studies investigating uptake transporter-enzyme interactions using cellular, perfused rat liver and intact rats are reviewed, followed by the human transporter-enzyme interaction studies. Work characterizing the rate limiting processes in the drug transporter-metabolism alliance is then addressed, ending with a review of areas of the interplay that require further studies and analysis.

Bidirectional transport studies were conducted using Caco-2, MDCK, and MDCK-MDR1 to determine P-gp influences in lamivudine and zidovudine permeability and evaluate if zidovudine permeability changes with the increase of zidovudine concentration and/or by association of lamivudine. Transport of lamivudine and zidovudine separated and coadministrated across monolayers based on these cells were quantified using LC-MS-MS. Drug efflux by P-gp was inhibited using GG918. Bidirectional transport of lamivudine and zidovudine was performed across MDCK-MDR1 and Caco-2 cells. Statistically significant transport decrease in B --> A direction was observed using MDCK-MDR1 for zidovudine and MDCK-MDR1 and Caco-2 for lamivudine. Results show increased transport in B --> A and A --> B directions as concentration increases but data from P(app) increase in both directions for both drugs in Caco-2, decrease in MDCK, and does not change significantly in MDCK-MDR1. Zidovudine transport in A --> B direction increases when coadministrated with increasing lamivudine concentration but does not change significantly in B --> A direction. Zidovudine and lamivudine are P-gp substrates, but results assume that P-gp does not affect significantly lamivudine and zidovudine. Their transport in monolayers based on Caco-2 cells increase proportionally to concentration (in both directions) and zidovudine transport in Caco-2 cell monolayer does not show significant changes with lamivudine increasing concentrations.

BACKGROUND

There is growing interest in the interface between palliative care and other medical specialties, yet little is known about decision-making processes characterizing such collaborations. At the University of Alabama at Birmingham (UAB), the trauma-burn surgery and neurosurgery services frequently request consults from the palliative care team for patients with a sudden advanced illness from catastrophic injuries or physiologic insult.

OBJECTIVE

We explored surgeons' attitudes and decision-making practices regarding utilization of palliative and supportive care for patients with a sudden advanced illness from traumatic injury or physiologic insult at UAB Hospital, an American College of Surgeons certified level 1 trauma center.

DESIGN AND ANALYSIS

We conducted face-to-face, open-ended interviews with nine attending trauma-burn surgeons and neurosurgeons at UAB, utilizing a grounded theory approach to discover salient themes in surgeons' accounts of the palliative care consultative process. Surgeons' descriptions of exemplary cases provided the context for elucidating the larger dynamic involved in assessing patients' situations and identifying the need for palliative and supportive care services.

RESULTS

We organized the data using decision-making diagrams, identifying multiple pathways within the larger consultative framework. Although case-based responses exhibited variations in surgeons diagnostic or prognostic criteria, patient's location in the illness/injury trajectory, and surgeon's goals/desired outcomes; a general decision-making pathway emerged.

CONCLUSIONS

Through collaboration with the palliative care service at UAB, trauma-burn surgeons and neurosurgeons are better equipped to manage the multidimensional nature of suffering and provide a holistic approach to care for patients and families dealing with a sudden advanced illness.