Publications

Fibrosis is characterized by accumulation of activated fibroblasts and pathological deposition of fibrillar collagens. Activated fibroblasts overexpress matrix proteins and release factors that promote further recruitment of activated fibroblasts, leading to progressive fibrosis. The contribution of epithelial cells to this process remains unknown. Epithelium-directed injury may lead to activation of epithelial cells with phenotypes and functions similar to activated fibroblasts. Prior reports that used a reporter gene fate-mapping strategy are limited in their ability to investigate the functional significance of epithelial cell-derived mesenchymal proteins during fibrogenesis. We found that lung epithelial cell-derived collagen I activates fibroblast collagen receptor discoidin domain receptor-2, contributes significantly to fibrogenesis, and promotes resolution of lung inflammation. Alveolar epithelial cells undergoing transforming growth factor-β-mediated mesenchymal transition express several other secreted profibrotic factors and are capable of activating lung fibroblasts. These studies provide direct evidence that activated epithelial cells produce mesenchymal proteins that initiate a cycle of fibrogenic effector cell activation, leading to progressive fibrosis. Therapy targeted at epithelial cell production of type I collagen offers a novel pathway for abrogating this progressive cycle and for limiting tissue fibrosis but may lead to sustained lung injury/inflammation.

INTRODUCTION

Advance directives have traditionally been considered the gold standard for advance care planning. However, recent evidence suggests that advance care planning involves a series of multiple discrete behaviors for which people are in varying stages of behavior change. The goal of our study was to develop and validate a survey to measure the full advance care planning process.

METHODS

The Advance Care Planning Engagement Survey assesses "Process Measures" of factors known from Behavior Change Theory to affect behavior (knowledge, contemplation, self-efficacy, and readiness, using 5-point Likert scales) and "Action Measures" (yes/no) of multiple behaviors related to surrogate decision makers, values and quality of life, flexibility for surrogate decision making, and informed decision making. We administered surveys at baseline and 1 week later to 50 diverse, older adults from San Francisco hospitals. Internal consistency reliability of Process Measures was assessed using Cronbach's alpha (only continuous variables) and test-retest reliability of Process and Action Measures was examined using intraclass correlations. For discriminant validity, we compared Process and Action Measure scores between this cohort and 20 healthy college students (mean age 23.2 years, SD 2.7).

RESULTS

Mean age was 69.3 (SD 10.5) and 42% were non-White. The survey took a mean of 21.4 minutes (±6.2) to administer. The survey had good internal consistency (Process Measures Cronbach's alpha, 0.94) and test-retest reliability (Process Measures intraclass correlation, 0.70; Action Measures, 0.87). Both Process and Action Measure scores were higher in the older than younger group, p<.001.

CONCLUSION

A new Advance Care Planning Engagement Survey that measures behavior change (knowledge, contemplation, self-efficacy, and readiness) and multiple advance care planning actions demonstrates good reliability and validity. Further research is needed to assess whether survey scores improve in response to advance care planning interventions and whether scores are associated with receipt of care consistent with one's wishes.

PURPOSE OF THE RESEARCH

To identify distinct latent classes of individuals based on ratings of morning and evening fatigue; evaluate for differences in phenotypic characteristics, as well as symptom and quality of life scores, among these latent classes; and evaluate for an overlap in morning and evening fatigue class membership.

PATIENTS AND METHODS

In a sample of 167 oncology outpatients and 85 of their FCs, growth mixture modeling was used to identify distinct latent classes based on ratings of morning and evening fatigue obtained before, during, and after radiation therapy. Analyses of variance and Chi Square analyses were used to evaluate for differences among the morning and evening fatigue latent classes.

RESULTS

Three distinct latent classes for morning fatigue were identified. Participants in the High Morning Fatigue class (47%) were younger and had lower functional status. Three distinct latent classes for evening fatigue were identified. Participants in the High Evening Fatigue class (61%) were younger, more likely to be female, more likely to have children at home, and more likely to be a FC. Only 10.3% of participants were classified in both the Very Low Morning and Low Evening Fatigue classes and 41.3% were classified in both the High Morning and High Evening Fatigue classes.

CONCLUSIONS

Different characteristics were associated with morning and evening fatigue, which suggests that morning and evening fatigue may be distinct but related symptoms. Additional research is needed to elucidate the mechanisms that may underlie diurnal variability in fatigue.

BACKGROUND

Small intestinal bacterial overgrowth (SIBO) is an under-recognised diagnosis with important clinical implications when untreated. However, the optimal treatment regimen remains unclear.

AIM

To perform a systematic review and meta-analysis comparing the clinical effectiveness of antibiotic therapies in the treatment of symptomatic patients with documented SIBO.

METHODS

Four databases were searched to identify clinical trials comparing effectiveness of: (i) different antibiotics, (ii) different doses of the same antibiotic and (iii) antibiotics compared with placebo. Data were independently extracted according to predetermined inclusion and exclusion criteria. Study quality was independently assessed. The primary outcome was normalisation of post-treatment breath testing. The secondary outcome was post-treatment clinical response.

RESULTS

Of 1356 articles identified, 10 met inclusion criteria. Rifaximin was the most commonly studied antibiotic (eight studies) with overall breath test normalisation rate of 49.5% (95% confidence interval, CI 44.0-55.1) (44.0%-55.1%) then (46.7%-55.5%), then (4.6%-17.8%). Antibiotic efficacy varied by antibiotic regimen and dose. Antibiotics were more effective than placebo, with a combined breath test normalisation rate of 51.1% (95% CI 46.7-55.5) for antibiotics compared with 9.8% (95% CI 4.6-17.8) for placebo. Meta-analysis of four studies favoured antibiotics over placebo for breath test normalisation with an odds ratio of 2.55 (95% CI 1.29-5.04). Clinical response was heterogeneously evaluated among six studies, but tended to correlate with breath test normalisation.

CONCLUSIONS

Antibiotics appear to be more effective than placebo for breath test normalisation in patients with symptoms attributable to SIBO, and breath test normalisation may correlate with clinical response. Studies were limited by modest quality, small sample size and heterogeneous design. Additional higher quality clinical trials of SIBO therapy are warranted.