Data on the benefit of selective serotonin reuptake inhibitors (SSRIs) in irritable bowel syndrome (IBS) are conflicting. The longitudinal relationship between clinical symptoms and sensitivity to ...barostat-mediated rectal distension in IBS remains unclear. We assessed the benefit of citalopram and explored the relationships between symptoms, quality of life (QOL), and rectal sensitivity to barostat distension in non-depressed IBS patients.
Patients from primary, secondary, and tertiary care settings were randomly assigned to receive citalopram (20 mg/day for 4 weeks, then 40 mg/day for 4 weeks) or placebo in a study with double-masking and concealed allocation. Symptoms were assessed weekly, and IBS-QOL and rectal sensation by barostat were assessed at the beginning and end of the study.
Patients receiving citalopram did not achieve a higher rate of adequate relief of IBS symptoms than patients receiving placebo (12/27 44% vs 15/27 56%; P = .59), regardless of IBS subtype. The odds ratio for weekly response with citalopram vs placebo was 0.80 (95% confidence interval, 0.61-1.04). Improvements in specific symptom and IBS-QOL scores were not superior for citalopram. Changes in IBS-QOL score and pressure eliciting pain showed a modest correlation (r = 0.33; 95% confidence interval, 0.03-0.57), but changes in symptoms and IBS-QOL scores or rectal sensitivity were not correlated substantially.
Citalopram was not superior to placebo in treating non-depressed IBS patients. Changes in symptoms were not substantially correlated with changes in rectal sensation assessed by barostat. Any benefit of citalopram in non-depressed IBS patients is likely to be modest at best.
The effectiveness of fecal immunochemical test (FIT) screening for colorectal cancer depends on timely colonoscopy follow-up of positive tests, although limited data exist regarding effective ...system-level strategies for improving follow-up rates.
Using a mixed-methods design (qualitative and quantitative), we first identified system-level strategies that were implemented for improving timely follow-up after a positive FIT test in a large community-based setting between 2006 and 2016. We then evaluated changes in time to colonoscopy among FIT-positive patients across 3 periods during the study interval, controlling for screening participant age, sex, race/ethnicity, comorbidity, FIT date, and previous screening history.
Implemented strategies over the study period included setting a goal of colonoscopy follow-up within 30 days of a positive FIT, tracking FIT-positive patients, early telephone contact to directly schedule follow-up colonoscopies, assigning the responsibility for follow-up tracking and scheduling to gastroenterology departments (vs primary care), and increasing colonoscopy capacity. Among 160,051 patients who had a positive FIT between 2006 and 2016, 126,420 (79%) had a follow-up colonoscopy within 180 days, including 67% in 2006-2008, 79% in 2009-2012, and 83% in 2013-2016 (P < 0.001). Follow-up within 180 days in 2016 varied moderately across service areas, between 72% (95% CI 70-75) and 88% (95% CI 86-91), but there were no obvious differences in the pattern of strategies implemented in higher- vs lower-performing service areas.
The implementation of system-level strategies coincided with substantial improvements in timely colonoscopy follow-up after a positive FIT. Intervention studies are needed to identify the most effective strategies for promoting timely follow-up.
Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal ...outreach, are not well known.
To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach.
This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test FIT kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023.
Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT.
The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test.
This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process.
In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.
Background
Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but ...whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population.
Aims
To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening.
Methods
FIT-negative and FIT-positive colorectal cancer patients 50–77 years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7
K-ras
mutations and 10 aberrantly methylated DNA biomarkers (
NDRG4
,
BMP3
,
SFMBT2_895
,
SFMBT2_896
,
SFMBT2_897
,
CHST2_7890
,
PDGFD
,
VAV3
,
DTX1
,
CHST2_7889
).
Results
One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher
SFMBT2_897
expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%;
p
= 0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups.
Conclusions
The biomarkers of a currently in-use multi-target stool DNA test (
K
-
ras
,
NDRG4
, and
BMP3
) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.
Cytochrome P450 1B1 (CYP1B1) plays an important role in breast cancer development and progression by bioactivating endogenous estrogens and environmental carcinogens. In this study, we examined the ...effect of the soy isoflavone genistein on CYP1B1 gene expression, reactive oxygen species (ROS) production, and cell proliferation in human breast cancer MCF-7 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed a dose-dependent induction of CYP1B1 gene expression in the cells treated with 5 and 25 μM of genistein. Genistein at 5 μM exhibited a synergistic effect on the CYP1B1 mRNA level induced by the environmental carcinogen 7,12-dimethylbenzaanthracene. We also found that genistein at 5 μM increased cellular levels of ROS and stimulated cell proliferation starting from the second day of culture. This study suggests that physiological concentrations of genistein stimulate ROS production and breast cancer cell proliferation through the induction of CYP1B1 gene expression. More extensive studies are warranted to further characterize the role of genistein and the CYP1B1 enzyme in human breast carcinogenesis.
Reliable estimates of adenoma detection rates (ADRs) are needed to inform colonoscopy quality standards, yet little is known about the contributions of patient demographics to variation in ADRs. We ...evaluated the effects of adjusting for patient age, race/ethnicity, and family history of colorectal cancer on variations in ADRs and the relative rank order of physicians.
In a retrospective cohort study, we collected data from Kaiser Permanente Northern California members who were ≥ 50 years old who received colonoscopies from 2006 through 2008. We evaluated ADRs (before and after adjustment for age, sex, race/ethnicity, and family history of colorectal cancer) for 102 endoscopists who performed 108,662 total colonoscopies and 20,792 screening colonoscopies. Adenomas were identified from the pathology database, and cancers were detected by using the Kaiser Permanente Northern California cancer registry.
About two-thirds of examiners had unadjusted ADRs for screening exams that met gastroenterology society guidelines (>25% for men and >15% for women), although rates of detection varied widely (7.7%-61.5% for male patients and 1.7%-45.6% for female patients). Adjusting for case mix reduced the variation in detection rates (from 8-fold to 3-fold for male patients and from 27-fold to 5-fold for female patients), but the median change in physician order by detection rate was just 2 ranks, and few physicians changed quartiles of detection. For example, only 3 of 102 endoscopists moved into and 3 out of the lowest quartile of ADR.
In a community-based setting, most endoscopists met the ADR standards, although there was wide variation in ADRs, which was similar to that reported from academic and referral settings. Case-mix adjustment reduced variability but had only small effects on differences in ADRs between physicians, and only a small percentage of physicians changed quartiles of detection. Adjustments to ADRs are therefore likely only needed in settings in which physicians have very different patient demographics, such as in sex or age. Moderate differences in patient demographics between physicians are unlikely to substantially change rates of adenoma detection.
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