Publications

OBJECTIVES

The effectiveness of stool-based colorectal cancer (CRC) screening is contingent on colonoscopy completion in patients with an abnormal fecal immunochemical test (FIT). Understanding system and patient factors affecting follow-up of abnormal screening tests is essential to optimize care for high-risk cohorts.

METHODS

This retrospective cohort study was conducted in an integrated safety-net system comprised of 11 primary-care clinics and one Gastroenterology referral unit and included patients 50-75 years, with a positive FIT between April 2012 and February 2015.

RESULTS

Of the 2,238 patients identified, 1,245 (55.6%) completed their colonoscopy within 1-year of the positive FIT. The median time from positive FIT to colonoscopy was 184 days (interquartile range 140-232). Of the 13% of FIT positive patients not referred to gastroenterology, 49% lacked documentation addressing their abnormal result or counseling on the increased risk of CRC. Of the patients referred but who missed their appointments, 62% lacked documentation following up on the abnormal result in the absence of a completed colonoscopy. FIT positive patients never referred to gastroenterology or who missed their appointment after referrals were more likely to have comorbid conditions and documented illicit substance use compared with patients who completed a colonoscopy.

CONCLUSIONS

Despite access to colonoscopy and a shared electronic health record system, colonoscopy completion after an abnormal FIT is inadequate within this safety-net system. Inadequate follow-up is in part explained by inappropriate screening, but there is an absence of clear documentation and systematic workflow within both primary care and GI specialty care addressing abnormal FIT results.

INTRODUCTION

Chinese Americans have low colorectal cancer (CRC) screening rates. Evidence-based interventions to increase CRC screening in this population are lacking. This study aims to compare the efficacy of two interventions in increasing CRC screening among Chinese Americans.

DESIGN

Cluster randomized comparative trial.

SETTING/PARTICIPANTS

From 2010 to 2014, a community-academic team conducted this study in San Francisco, CA with Chinese Americans aged 50-75 years who spoke English, Cantonese, or Mandarin.

INTERVENTION

Lay health worker (LHW) intervention plus in-language brochure (LHW+Print) versus brochure (Print). LHWs in the LHW+Print arm were trained to teach participants about CRC in two small group sessions and two telephone calls.

MAIN OUTCOME MEASURES

Change in self-reports of ever having had CRC screening and being up to date for CRC screening from baseline to 6 months post-intervention. Statistical analysis was performed from 2014 to 2015.

RESULTS

This study recruited 58 LHWs, who in turn recruited 725 participants. The average age of the participants was 62.2 years, with 81.1% women and 99.4% foreign born. Knowledge increase was significant (p<0.002) for nine measures in the LHW+Print group and six in the Print group. Both groups had increases in having ever been screened for CRC (LHW+Print, 73.9%-88.3%, p<0.0001; Print, 72.3%-79.5%, p=0.0003) and being up to date for CRC screening (LHW+Print, 60.0%-78.1%, p<0.0001; Print, 58.1%-64.1%, p=0.0003). In multivariable analyses, the intervention OR for LHW+Print versus Print was 1.94 (95% CI=1.34, 2.79) for ever screening and 2.02 (95% CI=1.40, 2.90) for being up to date.

CONCLUSIONS

Both in-language print materials and LHW outreach plus print materials increased CRC screening among Chinese Americans. The combination of LHW+Print was more effective than Print alone. These findings can guide clinicians and policymakers in choosing appropriate interventions to increase CRC screening among Chinese American immigrants.

TRIAL REGISTRATION

This study is registered at www.clinicaltrials.gov NCT00947206.

BACKGROUND

HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population.

METHODS

We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.

RESULTS

12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.

CONCLUSIONS

HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.

Mast cells are located at host interfaces, such as the skin, and contribute to the first-line defense against pathogens by releasing soluble mediators, including those that induce itching and scratching behavior. Here, we show that delta-hemolysin (Hld) and phenol soluble modulins (PSMs) PSMα1 and PSMα3, but not alpha-hemolysin (Hla) or Panton-Valentine leukocidin (PVL), induce dose-dependent tryptase, and lactate dehydrogenase (LDH) release by the HMC-1 human mast cell line. Using supernatants from isogenic strains, we verified that tryptase and LDH release was Hld- and PSMα-dependent. PSMα1 and Hld production was detected in 65 and 17% of human -infected skin abscess specimens, respectively, but they were produced by all clinical isolates. The results suggest that Hld and PSM-α1 produced during skin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission of the hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission of strains with a functional agr system.