Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin.

OBJECTIVE: A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy. DESIGN: We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints. RESULTS: At 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=-0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention. CONCLUSIONS: We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice. TRIAL NUMBER: NCT00468910.

A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast.

PURPOSE: Local transdermal therapy to the breast may achieve effective target-organ drug delivery, while diminishing systemic effects. We conducted a randomized, double-blind, placebo-controlled phase II trial comparing transdermal 4-hydroxytamoxifen gel (4-OHT) to oral tamoxifen (oral-T) in women with ductal carcinoma in situ (DCIS). METHODS: Twenty-seven pre- and postmenopausal women were randomized to 4-OHT (4 mg/day) or oral-T (20 mg/day) for 6 to 10 weeks before surgery. Plasma, nipple aspirate fluid, and breast adipose tissue concentrations of tamoxifen and its major metabolites were determined by liquid chromatography/tandem mass spectrometry. The primary endpoint was Ki67 labeling in DCIS lesions, measured by immunohistochemistry. In plasma, insulin-like growth factor-1 (IGFI), sex hormone-binding globulin (SHBG), and coagulation protein concentrations were determined. RESULTS: Posttherapy Ki67 decreased by 3.4% in the 4-OHT and 5.1% in the oral-T group (P ≤ 0.03 in both, between-group P = 0. 99). Mean plasma 4-OHT was 0.2 and 1.1 ng/mL in 4-OHT and oral groups, respectively (P = 0.0003), whereas mean breast adipose tissue concentrations of 4-OHT were 5.8 ng/g in the 4-OHT group and 5.4 ng/g in the oral group (P = 0.88). There were significant increases in plasma SHBG, factor VIII, and von Willebrand factor and a significant decrease in plasma IGFI with oral-T, but not with 4-OHT. The incidence of hot flashes was similar in both groups. CONCLUSIONS: The antiproliferative effect of 4-OHT gel applied to breast skin was similar to that of oral-T, but effects on endocrine and coagulation parameters were reduced. These findings support the further evaluation of local transdermal therapy for DCIS and breast cancer prevention.

A phase I trial of aminolevulinic acid-photodynamic therapy for treatment of oral leukoplakia.

BACKGROUND: Photodynamic therapy with aminolevulinic acid (ALA PDT) for oral leukoplakia has shown promising effects in regression of oral leukoplakia. Although ALA has been extensively studied and is an ideal photosensitizer, the optimal light dose for treatment of oral leukoplakia has not been determined. We conducted a phase I study to determine MTD and DLT of PDT in patients treated with ALA for leukoplakia. METHODS: Patients with histologically confirmed oral leukoplakia received a single treatment of ALA PDT in cohorts with escalating doses of light (585nm). Clinical, histologic, and biologic markers were assessed. RESULTS: Analysis of 11 participants is reported. No significant toxicity from ALA PDT was observed in patients who received ALA with a light dose of up to 4J/cm(2). One participant experienced transient grade 3 transaminase elevation due to ALA. One participant had a partial clinical response 3months after treatment. Biologic mucosal risk markers showed no significant associations. Determination of MTD could not be accomplished within a feasible timeframe for completion of the study. CONCLUSIONS: ALA PDT could be safely administered with a light dose up to 4J/cm(2) and demonstrated activity. Larger studies are needed to fully elucidate the MTD and efficacy of ALA-PDT.

Measuring adult literacy in health care: performance of the newest vital sign.

OBJECTIVE: To compare performance of the newest vital sign (NVS) with existing literacy measures. METHODS: We administered the NVS and REALM to 129 patients, and NVS and S-TOFHLA to 119 patients all in public clinics. RESULTS: The NVS demonstrated high sensitivity for detecting limited literacy and moderate specificity (area under the receiver operating characteristic [AUROC] curve 0.71-0.73). The NVS was less effective than the S-TOFHLA for predicting health outcomes. CONCLUSION: The NVS is able to identify patients with limited literacy skills, but may misclassify those with adequate literacy according to the REALM and S-TOFHLA. NVS scores were not associated with health outcomes.

Limited health literacy is a barrier to medication reconciliation in ambulatory care.

BACKGROUND: Limited health literacy may influence patients' ability to identify medications taken; a serious concern for ambulatory safety and quality. OBJECTIVE: To assess the relationship between health literacy, patient recall of antihypertensive medications, and reconciliation between patient self-report and the medical record. DESIGN: In-person interviews, literacy assessment, medical records abstraction. PARTICIPANTS: Adults with hypertension at three community health centers. MEASUREMENT: We measured health literacy using the short-form Test of Functional Health Literacy in Adults. Patients were asked about the medications they took for blood pressure. Their responses were compared with the medical record. RESULTS: Of 119 participants, 37 (31%) had inadequate health literacy. Patients with inadequate health literacy were less able to name any of their antihypertensive medications compared to those with adequate health literacy (40.5% vs 68.3%, p = 0.005). After adjusting for age and income, this difference remained (adjusted odds ratio [OR] = 2.9, 95% confidence interval [95%CI] = 1.3-6.7). Agreement between patient reported medications and the medical record was low: 64.9% of patients with inadequate and 37.8% with adequate literacy had no medications common to both lists. CONCLUSIONS: Limited health literacy was associated with a greater number of unreconciled medications. Future studies should investigate how this may impact safety and hypertension control.

Improving colorectal cancer screening among the medically underserved: a pilot study within a federally qualified health center.

BACKGROUND: Colorectal cancer screening rates remain low, especially among low-income and racial/ethnic minority groups. OBJECTIVE: We pilot-tested a physician-directed strategy aimed at improving rates of recommendation and patient colorectal cancer screening completion at 1 federally qualified health center serving low-income, African-American and Hispanic patients. Colonoscopy was specifically targeted. DESIGN: Single arm, pretest-posttest design. SETTING: Urban. PATIENTS: 154 screening-eligible, yet nonadherent primary care patients receiving care at an urban, federally qualified health center. INTERVENTION: 1) manually tracking screening-eligible patients, 2) mailing patients a physician letter and brochure before medical visits, 3) health literacy training to help physicians improve their communication with patients to work to resolution, and 4) establishing a "feedback loop" to routinely monitor patient compliance. MEASUREMENT: Chart review of whether patients received a physician recommendation for screening, and completion of any colorectal cancer screening test 12 months after intervention. Physicians recorded patients' qualitative reasons for noncompliance, and a preliminary cost-effectiveness analysis for screening promotion was also conducted. RESULTS: The baseline screening rate was 11.5%, with 31.6% of patients having received a recommendation from their physician. At 1-year follow-up, rates of screening completion had increased to 27.9 percent (p < .001), and physician recommendation had increased to 92.9% (p < .001). Common reasons for nonadherence included patient readiness (60.7%), competing health problems (11.9%), and fear or anxiety concerning the procedure (8.3%). The total cost for implementing the intervention was $4,676 and the incremental cost-effectiveness ratio for the intervention was $106 per additional patient screened by colonoscopy. CONCLUSIONS: The intervention appears to be a feasible means to improve colorectal cancer screening rates among patients served by community health centers. However, more attention to patient decision making and education may be needed to further increase screening rates.

Literacy, self-efficacy, and HIV medication adherence.

OBJECTIVE: We examined the relationship between patient literacy level and self-reported HIV medication adherence, while estimating the mediating roles of treatment knowledge and self-efficacy on this relationship. METHODS: Structured patient interviews with a literacy assessment, supplemented by medical chart review, were conducted among 204 consecutive patients receiving care at infectious disease clinics in Shreveport, Louisiana and Chicago, Illinois. Literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM), while the Patient Medication Adherence Questionnaire (PMAQ) was used to assess medication self-efficacy and adherence to antiretroviral regimens in the past 4 days. RESULTS: Approximately one-third of patients (30.4%) were less than 100% adherent to their regimen, and 31.4% had marginal to low literacy skills. In multivariate analyses, low literate patients were 3.3 times more likely to be non-adherent to their antiretroviral regimen (p < 0.001). Patients' self-efficacy, but not knowledge, mediated the impact of low literacy on medication adherence (AOR 7.4, 95% CI 2.7-12.5). CONCLUSION: While low literacy was a significant risk factor for improper adherence to HIV medication regimens in our study, self-efficacy mediated this relationship. PRACTICE IMPLICATIONS: Comprehensive intervention strategies that go beyond knowledge transfer may be needed to address self-efficacy among patients across all literacy levels to be successful in the management of difficult medication schedules.

Social stigma concerns and HIV medication adherence.

The threat of social stigma may prevent people living with HIV from revealing their status to others and serve as a barrier to HIV treatment adherence. We evaluated the effect of such concerns on self-reported treatment adherence using a short, three-item measure among 204 people living with HIV. Overall, the mean age of participants was 40.1 years, 45% were African American, and 80% were male. People with high HIV stigma concerns were 2.5 times less likely to define and interpret the meaning of CD4 count correctly and 3.3 times more likely to be nonadherent to their medication regimen than those with low concerns. Concern over revealing HIV status was the only statistically significant, independent predictor of adherence in multivariate analysis. Clinical care directed to individuals living with HIV should therefore include considerations for patient sensitivity to social stigma, such as modifications to medication schedules and referrals for counseling prior to enrollment in antiretroviral therapies.

Colorectal cancer screening among the medically underserved.

Prevalence of physician recommendation and patient completion of colorectal cancer screening was investigated among Federally Qualified Health Centers (FQHC) serving low-income neighborhoods in Chicago. Medical records of 3,416 patients receiving primary care services at 1 of 31 FQHCs were randomly chosen for review. In all, 642 patients were identified by age and family history as eligible for colorectal cancer screening and included in this study. Patient demographic information and colorectal cancer screening history were collected. The physician screening recommendation rate was 9.2% (n=59); 7.0% (n=45) of patients were determined to have been appropriately screened for colorectal cancer, primarily by Fecal Occult Blood Test (94.1%, n=43). Among patients who received a recommendation from their physician, 76.2% had completed a screening test. Older patients were more likely than their younger counterparts to have received a recommendation from their physician (p<.05) and to have been screened (p<.01). Organizational interventions are needed to support physicians in medically underserved areas and to promote recommended screening practices.