Publications

A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells. mTOR inhibitors suppress HIV transcription both through the viral transactivator Tat and via Tat-independent mechanisms. This inhibition occurs at least in part via blocking the phosphorylation of CDK9, a p-TEFb complex member that serves as a cofactor for Tat-mediated transcription. The control of HIV latency by mTOR signaling identifies a pathway that may have significant therapeutic opportunities.

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.