Blood-based colorectal cancer screening in an integrated health system: a randomised trial of patient adherence.

OBJECTIVE: We evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters. Blood-based screening tests for CRC could add to the total number of people screened for CRC by providing another testing alternative. DESIGN: Study participants were patients aged 45-75 years at a large, integrated health system who were offered but did not complete an FIT in the prior 3-9 months and were scheduled for a clinical encounter. Individuals were randomised (1:1) to be offered a commercially available CRC blood test (Shield, Guardant Health) versus usual care. We compared 3-month CRC screening proportions in the two groups. RESULTS: We randomised 2026 patients; 2004 remained eligible following postrandomisation exclusions (1003 to usual care and 1001 to blood draw offer; mean age: 60, 62% female, 80% non-Hispanic white). Of the 1001 allocated to the blood test group, 924 were recruited following chart-review exclusions; 548 (59.3%) were reached via phone, of which 280 (51.1%) scheduled an appointment with the research team. CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001). CONCLUSION: Among adults who had declined prior CRC screening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care. Further research is needed on how to balance the favourable adherence with lower advanced adenoma detection compared with other available tests. TRIAL REGISTRATION NUMBER: NCT05987709.

Burden of Medically Attended Diarrhea and Outpatient Clostridioides difficile Infection Among Persons in 2 Large Integrated Healthcare Settings, 2016-2021.

Background: Identification of Clostridioides difficile infection (CDI) in the community setting is increasing. We describe testing for CDI among patients with medically attended diarrhea (MAD) in the outpatient setting, and the incidence of outpatient CDI. Methods: This was a retrospective cohort study among members ≥18 years of age from Kaiser Permanente Southern California and Kaiser Permanente Northwest from 1 January 2016 through 31 December 2021. MAD was identified by outpatient diarrheal International Classification of Diseases, Tenth Revision diagnosis codes, and CDI through positive laboratory results. Outpatient CDI was defined by no hospitalization ≤7 days after specimen collection. Incidence rates (IRs) of outpatient CDI were stratified by select demographic and clinical variables. Outpatient CDI burden 12 months following index date was measured by CDI-associated healthcare visits, and CDI testing and treatment. Results: We identified 777 533 MAD episodes; 12.1% (93 964/777 533) were tested for CDI. Of those tested, 10.8% (10 110/93 964) were positive. Outpatient CDI IR was 51.0 (95% confidence interval [CI], 49.8-52.2) per 100 000 person-years, decreasing from 58.2 (95% CI, 55.7-60.7) in 2016 to 45.7 (95% CI, 43.7-47.8) in 2021. Approximately 44% (n = 4200) received an antibiotic 30 days prior to index date and 84.1% (n = 8006) CDIs were "community-associated" (no hospitalizations 12 weeks prior to index date). Of outpatient CDIs, 6.7% (n = 526) had a CDI-associated hospitalization ≤12 months. Conclusions: There was a high incidence of outpatient CDI despite infrequent CDI testing among patients with MAD. The majority of those with outpatient CDI had no recent antibiotic use and no recent hospitalization. Further studies are needed to understand the source and management of medically attended outpatient CDI.

Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system.

INTRODUCTION: Lynch syndrome (LS) is associated with an increased risk of colorectal (CRC) and endometrial (EC) cancers. Universal tumor screening (UTS) of all individuals diagnosed with CRC and EC is recommended to increase identification of LS. Kaiser Permanente Northwest (KPNW) implemented a UTS program for LS among individuals newly diagnosed with CRC in January 2016 and EC in November 2016. UTS at KPNW begins with immunohistochemistry (IHC) of tumor tissue to determine loss of mismatch repair proteins associated with LS (MLH1, MSH2, MSH6, and PMS2)., IHC showing loss of MLH1 is followed by reflex testing (automatic testing) to detect the presence of the BRAF V600E variant (in cases of CRC) and MLH1 promoter hypermethylation to rule out likely sporadic cases. MATERIALS AND METHODS: Individuals newly diagnosed with CRC and EC were identified between the initiation of the respective UTS programs and July 2018. Electronic medical records were reviewed to extract patient data related to UTS, including IHC and reflex testing results, date of referrals to the genetics department, and results of germline genetic testing for LS. RESULTS: 313 out of 362 individuals diagnosed with CRC and 61 out of 64 individuals diagnosed with EC who were eligible were screened by IHC for LS. Most (47/52 or 90%, including 46/49 CRC and 1/3 EC) individuals that were not screened by IHC only had a biopsy sample available. Fourteen individuals (3.7% overall, including 13/313 CRC and 1/61 EC) received an abnormal result after reflex testing and were referred for genetic counseling. Of these, 10 individuals (71% overall, including 9/13 CRC and 1/1 EC) underwent germline genetic testing for LS. Five individuals diagnosed with CRC were found to have pathogenic variants. in PMS2 (n = 3), MLH1 (n = 1), and MSH6 (n = 1). No pathogenic variants were identified in individuals diagnosed with EC. CONCLUSIONS: UTS identified individuals at risk for LS. Most individuals who screened positive for LS had follow-up germline genetic testing for LS. The consistent use of biopsy samples is an opportunity to improve UTS.

Retrospective assessment of barriers and access to genetic services for hereditary cancer syndromes in an integrated health care delivery system.

BACKGROUND: A critical step in access to genetic testing for hereditary cancer syndromes is referral for genetic counseling to assess personal and family risk. Individuals meeting testing guidelines have the greatest need to be evaluated. However, referrals to genetics are underutilized in US patients with hereditary cancer syndromes, especially within traditionally underserved populations, including racial and ethnic minorities, low-income, and non-English speaking patients. METHODS: We studied existing processes for referral to genetic evaluation and testing for hereditary cancer risk to identify areas of potential improvement in delivering these services, especially for traditionally underserved patients. We conducted a retrospective review of 820 referrals to the Kaiser Permanente Northwest (KPNW) genetics department containing diagnosis codes for hereditary cancer risk. We classified referrals as high- or low-quality based on whether sufficient information was provided to determine if patients met national practice guidelines for testing. Through chart abstraction, we also assessed consistency with practice guidelines, whether the referral resulted in a visit to the genetics department for evaluation, and clinical characteristics of patients receiving genetic testing. RESULTS: Most referrals (n = 514, 63%) contained sufficient information to assess the appropriateness of referral; of those, 92% met practice guidelines for genetic testing. Half of referred patients (50%) were not offered genetic evaluation; only 31% received genetic testing. We identified several barriers to receiving genetic evaluation and testing, the biggest barrier being completion of a family history form sent to patients following the referral. Those with a referral consistent with testing guidelines, were more likely to receive genetic testing than those without (39% vs. 29%, respectively; p = 0.0058). Traditionally underserved patients were underrepresented in those receiving genetic evaluation and testing relative to the overall adult KPNW population. CONCLUSIONS: Process improvements are needed to increase access to genetic services to diagnose hereditary cancer syndromes prior to development of cancer.

Implementation of a Systematic Tumor Screening Program for Lynch Syndrome in an Integrated Health Care Setting.

A subset of colorectal cancer (CRC) cases are attributable to Lynch syndrome (LS), a hereditary form of CRC. Effective evaluation for LS can be done on CRC tumors to guide diagnostic testing. Increased diagnosis of LS allows for surveillance and risk reduction, which can mitigate CRC-related burden and prevent cancer-related deaths. We evaluated participation in LS screening among newly diagnosed adult CRC patients. Some cases were referred for genetics evaluation prior to study recruitment (selective screening). Those not referred directly were randomized to the intervention or control (usual care) arms. Control cases were observed for one year, then given information about LS screening. Patients who declined participation were followed through the medical record. Of 601 cases of CRC, 194 (32%) enrolled in our study and were offered LS screening, 43 (7%) were followed as a control group, 148 (25%) declined participation and 216 (36%) were ineligible [63 (10%) of which received prior selective screening]. Six and nine cases of LS were identified through the intervention and selective screening groups, respectively. Overall, a higher proportion of PMS2 variants were identified in the intervention (3/6, 50%) versus selective screening groups (2/9, 22%) (not statistically significant). Eighty-eight percent and 23% of intervention and control patients, respectively, received LS screening. No control patients were found to have LS. Systems-based approaches are needed to ensure we fully identify LS cases. The proportion of LS cases from this program was 4% of newly diagnosed cases of CRC, similar to other programs.

Recommended care and care adherence following a diagnosis of Lynch syndrome: a mixed-methods study.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This study assesses trends in diagnosis of LS and adherence to recommended LS-related care in a large integrated healthcare organization (~ 575,000 members). METHODS: Electronic medical record (EMR) data (1999-2015) were examined to identify patients with a diagnosis of LS. We examined their LS-associated care recommendations and adherence to these recommendations. Qualitative patient and provider interviews were conducted with the aim of identifying opportunities for improved care delivery. RESULTS: We identified 74 patients with a diagnosis of LS; 64% were diagnosed with a LS-related malignancy prior to their diagnosis of LS. The time to LS diagnosis following development of a LS-related cancer decreased over time: before 2009 11% of individuals received a diagnosis of LS within 1 year of developing a LS-related cancer compared to 83% after 2009 (p < 0.0001). Colonoscopy recommendations were documented in the EMR for almost all patients with LS (96%). Documentation of other recommendations for cancer surveillance was less commonly found. Overall, patient adherence to colonoscopy was high (M = 81.5%; SD = 32.7%), and adherence to other recommendations varied. To improve care coordination, patients and providers suggested providing automated reminder prompts for LS-related surveillance, adding a LS-specific diagnosis code, and providing guidelines for LS-related surveillance in the EMR. CONCLUSIONS: We identified fewer than expected patients with LS in our large care system, indicating that there is still a diagnostic care gap. However, patients with LS were likely to receive and follow CRC surveillance recommendations. Recommendations for and adherence to extracolonic surveillance were variable. Improved care coordination and clearer documentation of the LS diagnosis is needed.