Assessing the Impact of COVID-19 on IBD Outcomes Among Vulnerable Patient Populations in a Large Metropolitan Center.

BACKGROUND: With the onset of COVID-19, there were rapid changes in healthcare delivery as remote access became the norm. The aim of this study was to determine the impact of changes in healthcare delivery during the COVID-19 pandemic on patients with inflammatory bowel disease (IBD), in both well-resourced and vulnerable populations. METHODS: Using a mixed methods, observational study design, patients receiving IBD care at a university or a safety-net hospital were identified by the electronic health record. Patient demographics, IBD history, and disease activity were acquired from the electronic health record. IBD-related outcomes were compared from the onset of the pandemic in the United States until December 2020 (COVID-19 pandemic year 1) and compared with outcomes in the previous year. A subset of participants provided their perspective on how changes in healthcare delivery and financial stability impacted their IBD through a standardized questionnaire and semi-structured interview. RESULTS: Data from a total of 1449 participants were captured, 1324 at the tertiary care university hospital and 125 at the safety-net hospital. During COVID-19, there was a decrease in healthcare utilization at both sites. Race/ethnicity and primary language were not associated with IBD-related hospitalizations or admissions. Patients that were employed and those with insurance had a higher number of IBD-related emergency department visits at both the university and safety-net hospitals (P = .03 and P = .01, respectively). Patients who did not speak English were more likely to report challenges using technology with telehealth and difficulty contacting IBD providers. CONCLUSIONS: For IBD populations, during COVID-19, in both hospital settings, emergency department visits, hospitalizations, outpatient surgery, and clinic visits were reduced compared with the year prior. Patients with lower socioeconomic status and limited English proficiency reported facing more challenges with changes to healthcare delivery, healthcare access, and conveying changes in IBD activity. These results highlight the need for payors and providers to specifically attend to those populations most susceptible to these systemic and lasting changes in care delivery and promote greater equity in healthcare.

Intestinal Metaplasia Associated with Symptoms of Dyspepsia.

Background: Peptic ulcer disease (PUD) and Helicobacter pylori (HP) are associated with dyspepsia, but the role of gastric intestinal metaplasia (IM) has not been described. The objective of this study is to examine the association between gastric IM and dyspepsia. Methods: We developed a cohort of consecutive patients referred to gastroenterology between Jan 2019 and July 2020 for dyspepsia and iron deficiency anemia (IDA) and completed an upper endoscopy with biopsies in a safety-net health system. The primary outcome was the prevalence of gastric IM in patients with dyspepsia compared to IDA. Secondary outcomes included prevalence of HP, chronic gastritis (CG) and chronic active gastritis (CAG) in the dyspepsia and IDA groups. A multivariable analysis was performed to assess the independent association between gastric IM and dyspepsia. Results: Compared to the IDA cohort (n = 366), patients with dyspepsia (n = 349) were more likely to be female (65% vs. 47%, p < 0.01), harbor gastric IM (20.3% vs. 14.2%, p = 0.03), and less likely to have CAG (12.0% vs. 26.5%, p < 0.01) or HP (10.9% vs. 21.3%, p < 0.01). After adjusting for pathological findings, race, ethnicity, gender and age, the association strengthened between IM and dyspepsia (adj OR 1.81 from OR 1.54, 95% CI 1.19-2.76, p < 0.01). Conclusions: We observed a significant relationship between the presence of gastric IM and dyspepsia symptoms, which increased after adjusting for confounding factors. Future studies should verify the relationship between IM and dyspepsia, the effect of IM regression, and possible mediators of gastric IM on symptoms.

Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19.

The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.

The human microbiome and gut-liver axis in people living with HIV.

PURPOSE OF REVIEW: Chronic liver disease is a major cause of morbidity and mortality amongst people living with HIV (PLWH). Emerging data suggests that gut microbial translocation may play a role in driving and modulating liver disease, a bi-directional relationship termed the gut-liver axis. While it is recognized that PLWH have a high degree of dysbiosis and gut microbial translocation, little is known about the gut-liver axis in PLWH. RECENT FINDINGS: Recent studies have shown that microbial translocation can directly lead to hepatic inflammation, and have linked gut microbial signatures, dysbiosis, and translocation to liver disease in PLWH. Additionally, multiple trials have explored interventions targeting the microbiome in PLWH. Emerging research supports the interaction between the gut microbiome and liver disease in PLWH. This offers new opportunities to expand our understanding of the pathophysiology of liver disease in this population, as well as to explore possible clinical interventions.

Implementation of a novel program to support colorectal cancer screening in a community health center consortium before and after the onset of COVID-19: a qualitative study of stakeholders' perspectives.

BACKGROUND: In 2017, the San Francisco Cancer Initiative (SF CAN) established the Colorectal Cancer (CRC) Screening Program to provide technical assistance and financial support to improve CRC screening processes, and outcomes in a consortium of community health centers (CHCs) serving low-income communities in San Francisco. The purpose of this study was twofold: to evaluate the perceived influence of the support provided by the CRC Screening Program's Task Force on CRC screening processes and outcomes in these settings and to identify facilitators and barriers to SF CAN-supported CRC screening activities before and after the onset of the COVID-19 pandemic. METHODS: Semi-structured key informant interviews were conducted with consortium leaders, medical directors, quality improvement team members, and clinic screening champions. Interviews were audio-recorded, professionally transcribed, and analyzed for themes. The Consolidated Framework for Implementation Research (CFIR) was used to develop the interview questions and organize the analysis. RESULTS: Twenty-two participants were interviewed. The most commonly cited facilitators of improved screening processes included the expertise, funding, screening resources, regular follow-up, and sustained engagement with clinic leaders provided by the task force. The most salient barriers identified were patient characteristics, such as housing instability; staffing challenges, such as being understaffed and experiencing high staff turnover; and clinic-level challenges, such as lack of ability to implement and sustain formalized patient navigation strategies, and changes in clinic priorities due to the COVID-19 pandemic and other competing health care priorities. CONCLUSIONS: Implementing CRC screening programs in a consortium of CHCs is inherently challenging. Technical assistance from the Task Force was viewed positively and helped to mitigate challenges both before and during the pandemic. Future research should explore opportunities to increase the robustness of technical assistance offered by groups such as SF CAN to support cancer screening activities in CHCs serving low-income communities.

Effect of Mailed Fecal Immunochemical Test Outreach for Patients Newly Eligible for Colorectal Cancer Screening.

INTRODUCTION: Limited data exists on the effectiveness of organized outreach campaigns on CRC screening completion for patients who are newly eligible for such screening. METHODS: We conducted an analysis of an existing clinical trial dataset of a publicly funded safety-net health system serving low-income populations. RESULTS: A total of 619 patients aged 50-51 received the outreach intervention and 3108 patients aged greater than 51 years old who had no prior history of FIT testing similarly received the outreach intervention. Patients newly eligible for FIT were more likely to complete a FIT test compared with older patients who had yet to complete a FIT test (58.3% vs 40.5%, p < 0.001). CONCLUSION: Patients who are newly eligible for colorectal cancer screening are more likely to respond to outreach interventions than older patients without a prior history of FIT, indicating newly eligible patients across diverse populations may benefit from targeted outreach intervention.

Neighborhood socioeconomic status and the effectiveness of colorectal cancer screening outreach with mailed fecal immunochemical tests within a safety net healthcare system in San Francisco, CA: A subgroup analysis of a randomized controlled trial.

Neighborhood context shapes opportunities and barriers for residents to access healthcare and cancer screening. Neighborhood socioeconomic status (nSES) is associated with disparities in colorectal cancer (CRC) screening, but the extent to which the effectiveness of specific screening interventions vary by nSES has not been studied. The original trial conducted in San Francisco, CA from 2016 to 2017 randomly assigned patients eligible for CRC screening either to a multicomponent intervention including advanced notification, mailed fecal immunochemical test (FIT) kits and reminders or to a control group receiving usual care. For the nSES analysis addresses for 9699 patients were geocoded and stratified by city-wide nSES quintile (Q1 lowest, Q5 highest) using an established index at the census tract level. Compared to usual care, the outreach intervention improved FIT test completion at one year (58.7% vs 38.4%; OR 2.32 [2.14, 2.52]) but its effectiveness did not vary substantially by nSES quintile (adjusted OR Q1 2.64 [2.30, 3.04]; Q2 2.43 [2.04, 2.90]; Q3 2.31 [1.84, 2.89]; Q4 2.47 [1.86, 3.28]; Q5 2.64 [1.83, 3.81]; Wald test for interaction p = 0.87). The implementation of mailed FIT outreach has the potential to increase CRC screening completion without leading to disparities in screening related to nSES (ClinicalTrials.gov NCT02613260).

Durability of FIT Screening After Cessation of a Screening Outreach Intervention.

INTRODUCTION: Organized outreach to increase CRC screening using mailed FIT tests has been shown to be effective, but durable changes to screening behavior after cessation of screening is not known. METHODS: In this study, after cessation of funding for an organized cancer screening outreach program, we evaluated whether adherence to screening remained elevated. Patients aged 50-75 years eligible for CRC screening from eight safety net clinics were randomly assigned to outreach intervention vs usual care alone in 2016 to 2018; the primary outcome analyzed was the difference in the cumulative proportion of completed FIT screening between study assignments 1 year after study cessation. RESULTS: Despite higher rates of FIT screening for patients who were randomly assigned to the outreach intervention, FIT completion was not significantly different between the group that received the outreach services versus the usual care group (28.3% vs 29.8%, p = 0.158). CONCLUSION: Outreach campaigns and their activities must be sustained to maintain improved rates of screening participation.

Extent of Follow-Up on Abnormal Cancer Screening in Multiple California Public Hospital Systems: A Retrospective Review.

BACKGROUND: Inequitable follow-up of abnormal cancer screening tests may contribute to racial/ethnic disparities in colon and breast cancer outcomes. However, few multi-site studies have examined follow-up of abnormal cancer screening tests and it is unknown if racial/ethnic disparities exist. OBJECTIVE: This report describes patterns of performance on follow-up of abnormal colon and breast cancer screening tests and explores the extent to which racial/ethnic disparities exist in public hospital systems. DESIGN: We conducted a retrospective cohort study using data from five California public hospital systems. We used multivariable robust Poisson regression analyses to examine whether patient-level factors or site predicted receipt of follow-up test. MAIN MEASURES: Using data from five public hospital systems between July 2015 and June 2017, we assessed follow-up of two screening results: (1) colonoscopy after positive fecal immunochemical tests (FIT) and (2) tissue biopsy within 21 days after a BIRADS 4/5 mammogram. KEY RESULTS: Of 4132 abnormal FITs, 1736 (42%) received a follow-up colonoscopy. Older age, Medicaid insurance, lack of insurance, English language, and site were negatively associated with follow-up colonoscopy, while Hispanic ethnicity and Asian race were positively associated with follow-up colonoscopy. Of 1702 BIRADS 4/5 mammograms, 1082 (64%) received a timely biopsy; only site was associated with timely follow-up biopsy. CONCLUSION: Despite the vulnerabilities of public-hospital-system patients, follow-up of abnormal cancer screening tests occurs at rates similar to that of patients in other healthcare settings, with colon cancer screening test follow-up occurring at lower rates than follow-up of breast cancer screening tests. Site-level factors have larger, more consistent impact on follow-up rates than patient sociodemographic traits. Resources are needed to identify health system-level factors, such as test follow-up processes or data infrastructure, that improve abnormal cancer screening test follow-up so that effective health system-level interventions can be evaluated and disseminated.

Determinants of Colorectal Cancer Screening among South Asian Americans.

BACKGROUND: Colorectal cancer screening rates among South Asian Americans are among the lowest of US population groups. Few population-based studies have examined determinants of screening in this population. The purpose of this study was to identify factors associated with colorectal cancer screening among South Asian Americans. METHODS: Data from the 2001-2009 California Health Interview Survey and multivariable logistic regression were used to examine determinants of being non-adherent with colorectal cancer screening recommendations. Independent variables include sociodemographic and healthcare access measures. RESULTS: Overall, 49% of 459 South Asian Americans were non-adherent to screening recommendations. Characteristics associated with non-adherence were the absence of flu shot, absence of doctor visits, sole use of non-English language at home and ≤40% life spent in the United States. In the multivariable model, screening non-adherence was associated with ≤40% life in the United States (odds ratio [95% confidence interval] 3.0 [1.4-6.5]), use of non-English at home (2.8 [1.0-7.8]) and no flu shot (2.5 [1.3-4.8]). Obese (BMI > 27.5 kg/m2) versus normal-weight patients were less likely to be non-adherent (0.4 [0.2-0.9]). CONCLUSIONS: Length of time in the United States and language spoken at home rather than English proficiency were associated with non-adherence to colorectal cancer screening, reflecting the importance of acculturation and retention of cultural values. Health conditions and behaviors reflecting more proactive healthcare utilization may reinforce the importance of provider recommendations and perceived efficacy of health prevention. Qualitative research would inform cultural tailoring necessary to improve colorectal cancer screening rates among the rapidly growing South Asian American population.

LOXL-2 and TNC-C are markers of liver fibrogenesis in HCV/HIV-, HIV- and HCV-infected patients.

Background: Lysil oxidase like enzyme-2 (LOXL-2) and TNC-C play important roles in organ fibrosis. We assessed circulating LOXL-2 and TNC-C levels and their relationship to fibrosis severity in HIV- and/or HCV-infected individuals. Methods: Healthy controls (n = 22), HIV mono- (n = 15), HCV mono- (n = 52) and HCV/HIV-co-infected (n = 92) subjects were included. Results: LOXL-2 and TNC-C levels were significantly higher in HCV mono- and HCV/HIV-co-infected individuals with F0 compared to healthy controls. In addition, in HCV/HIV-co-infected individuals, LOXL-2 levels were higher in intermediate fibrosis compared to no/mild fibrosis. Conclusion: In HCV/HIV-co-infected study participants, both LOXL-2 and TNC-C were significantly higher in intermediate fibrosis compared to no/mild fibrosis, but did not further increase with advanced fibrosis. Furthermore, both markers were elevated among HCV/HIV-positive individuals with mild/no fibrosis.

Multiomic Analysis of the Gut Microbiome in Psoriasis Reveals Distinct Host‒Microbe Associations.

Psoriasis is a chronic, inflammatory skin disease that affects 2‒3% of the global population. Besides skin manifestations, patients with psoriasis have increased susceptibility to a number of comorbidities, including psoriatic arthritis, cardiovascular disease, and inflammatory bowel disease. To understand the systemic component of psoriasis pathogenesis, we performed a pilot study to examine the fecal metagenome, host colonic transcriptome, and host peripheral blood immune profiles of patients with psoriasis and healthy controls. Our study showed increased functional diversity in the gut microbiome of patients with psoriasis. In addition, we identified microbial species that preferentially associate with patients with psoriasis and which have been previously found to associate with other autoimmune diseases. Intriguingly, our data revealed three psoriasis subgroups that have distinct microbial and host features. Integrating these features revealed host‒microbe associations that are specific to psoriasis or particular psoriasis subgroups. Our findings provide insight into the factors that may affect the development of comorbidities in patients with psoriasis and may hold diagnostic potential for early identification of patients with psoriasis at risk for these comorbidities.

From Cancer Epidemiology to Policy and Practice: the Role of a Comprehensive Cancer Center.

Purpose of Review: Cancer incidence and mortality are decreasing, but inequities in outcomes persist. This paper describes the San Francisco Cancer Initiative (SF CAN) as a model for the systematic application of epidemiological evidence to reduce the cancer burden and associated inequities. Recent Findings: SF CAN is a multi-institutional implementation of existing evidence on the prevention and early detection of five common cancers (i.e., breast, prostate, colorectal, liver, and lung/tobacco-related cancers) accounting for 50% of cancer deaths in San Francisco. Five Task Forces follow individual logic models designating inputs, outputs, and outcomes. We describe the progress made and the challenges faced by each Task Force after 5 years of activity. Summary: SF CAN is a model for how the nation's Comprehensive Cancer Centers are ideally positioned to leverage cancer epidemiology for evidence-based initiatives that, along with genuine community engagement and multiple stakeholders, can reduce the population burden of cancer.

Increased Colorectal Cancer Screening Sustained with Mailed Fecal Immunochemical Test Outreach.

BACKGROUND & AIMS: Reports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics. METHODS: A total of 10,771 patients aged 50 to 75 years not up-to-date with colorectal cancer screening were randomized to intervention or usual care. The intervention arm received an advanced notification call and informational postcard prior to a mailed FIT. Usual care was at the discretion of the primary care provider. Patients were followed for up to 2.5 years. The primary outcome was the difference in cumulative proportion of completed FIT screening between arms. Screening was further examined with the proportion of time up-to-date, consistency of adherence, and frequency of abnormal FIT. RESULTS: The cumulative proportion of FIT completion was higher in the outreach intervention (73.2% vs 55.1%; P < .001). The proportion of time covered by screening was higher in the intervention group (46.8% vs 27.3%; Δ19.6%; 95% confidence interval, 18.2%-20.9%). Patients assigned to FIT outreach were more likely to consistently complete FITs (2 completed of 2 offered) (50.1% vs 21.8%; P < .001). However, for patients who did not complete the FIT during the first cycle, only 17.1% completed a FIT during the second outreach cycle. The number and overall proportion of abnormal FIT was significantly higher in the outreach intervention (6.9% Outreach vs 4.1% Usual Care; P < .01). CONCLUSIONS: Organized mailed FIT outreach significantly increased colorectal cancer screening over multiple years in this safety-net health system. Although mailing was overall effective, the effect was modest in patients who did not complete FIT in first cycle of intervention. (ClincialTrials.gov, NCT02613260).

Asian American/Pacific Islander and Hispanic Ethnic Enclaves, Neighborhood Socioeconomic Status, and Hepatocellular Carcinoma Incidence in California: An Update.

BACKGROUND: Using more recent cancer registry data, we analyzed disparities in hepatocellular carcinoma (HCC) incidence by ethnic enclave and neighborhood socioeconomic status (nSES) among Asian American/Pacific Islander (AAPI) and Hispanic populations in California. METHODS: Primary, invasive HCC cases were identified from the California Cancer Registry during 1988-1992, 1998-2002, and 2008-2012. Age-adjusted incidence rates (per 100,000 population), incidence rate ratios, and corresponding 95% confidence intervals were calculated for AAPI or Hispanic enclave, nSES, and the joint effects of ethnic enclave and nSES by time period (and the combination of the three periods), sex, and race/ethnicity. RESULTS: In the combined time period, HCC risk increased 25% for highest versus lowest quintile of AAPI enclave among AAPI males. HCC risk increased 22% and 56% for lowest versus highest quintile of nSES among AAPI females and males, respectively. In joint analysis, AAPI males living in low nSES areas irrespective of enclave status were at 17% to 43% increased HCC risk compared with AAPI males living in areas of nonenclave/high nSES. HCC risk increased by 22% for Hispanic females living in areas of low nSES irrespective of enclave status and by 19% for Hispanic males living in areas of nonenclave/low nSES compared with their counterparts living in areas of nonenclave/high nSES. CONCLUSIONS: We found significant variation in HCC incidence by ethnic enclave and nSES among AAPI and Hispanic populations in California by sex and time period. IMPACT: Future studies should explore how specific attributes of enclaves and nSES impact HCC risk for AAPI and Hispanic populations.

A Root Cause Analysis of Barriers to Timely Colonoscopy in California Safety-Net Health Systems.

OBJECTIVES: Safety-net health care systems, serving vulnerable populations, see longer delays to timely colonoscopy after a positive fecal occult blood test (FOBT), which may contribute to existing disparities. We sought to identify root causes of colonoscopy delay after positive FOBT result in the primary care safety net. METHODS: We conducted a multisite root cause analysis of cases of delayed colonoscopy, identifying cases where there was a delay of greater than 6 months in completing or scheduling a follow-up colonoscopy after a positive FOBT. We identified cases across 5 California health systems serving low-income, vulnerable populations. We developed a semistructured interview guide based on precedent work. We conducted telephone individual interviews with primary care providers (PCPs) and patients. We then performed qualitative content analysis of the interviews, using an integrated inductive-deductive analytic approach, to identify themes related to recurrent root causes of colonoscopy delay. RESULTS: We identified 12 unique cases, comprising 5 patient and 11 PCP interviews. Eight patients completed colonoscopy; median time to colonoscopy was 11.0 months (interquartile range, 6.3 months). Three patients had advanced adenomatous findings. Primary care providers highlighted system-level root causes, including inability to track referrals between primary care and gastroenterology, lack of protocols to follow up with patients, lack of electronic medical record interoperability, and lack of time or staffing resources, compelling tremendous additional effort by staff. In contrast, patients' highlighted individual-level root causes included comorbidities, social needs, and misunderstanding the importance of the FOBT. There was a little overlap between PCP and patient-elicited root causes. CONCLUSIONS: Current protocols do not accommodate communication between primary care and gastroenterology. Interventions to address specific barriers identified include improved interoperability between PCP and gastroenterology scheduling systems, protocols to follow-up on incomplete colonoscopies, accommodation for support and transport needs, and patient-friendly education. Interviewing both patients and PCPs leads to richer analysis of the root causes leading to delayed diagnosis of colorectal cancer.

Dual targeting of lymphocyte homing and retention through α4ß7 and αEß7 inhibition in inflammatory bowel disease.

Anti-integrins are therapeutically effective for inflammatory bowel disease, yet the relative contribution of α4ß7 and αEß7 to gut lymphocyte trafficking is not fully elucidated. Here, we evaluate the effect of α4ß7 and αEß7 blockade using a combination of murine models of gut trafficking and longitudinal gene expression analysis in etrolizumab-treated patients with Crohn's disease (CD). Dual blockade of α4ß7 and αEß7 reduces CD8+ T cell accumulation in the gut to a greater extent than blockade of either integrin alone. Anti-αEß7 reduces epithelial:T cell interactions and promotes egress of activated T cells from the mucosa into lymphatics. Inflammatory gene expression is greater in human intestinal αEß7+ T cells. Etrolizumab-treated patients with CD display a treatment-specific reduction in inflammatory and cytotoxic intraepithelial lymphocytes (IEL) genes. Concurrent blockade of α4ß7 and αEß7 promotes reduction of cytotoxic IELs and inflammatory T cells in the gut mucosa through a stepwise inhibition of intestinal tissue entry and retention.