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A limited pilot study has been made of a newly devised heparin reduction algorithm (HRA). This formulation is a derivative of the alternative surveillance plan known as the activated partial thromboplastin time after heparin removal (aPTT/HR) scheme. Unlike the traditional plan, the HRA is the first approach to provide information about the individual and collective pharmacological effects of heparin and coumarins when the drugs are administered simultaneously. In this feasibility study the HRA was used without incident in six patients every 24 h to calculate the trend of the evolving anticoagulant effect of coumarin. The computations provided by a laboratory based data management group permitted the clinician to titrate precisely the withdrawal of heparin in response to the daily fluctuations in coumarin effect. In this way, the activated partial thromboplastin time could always be maintained within the desired therapeutic interval. Three divergent patient experiences are presented to demonstrate the operational characteristics and responsiveness of the new HRA plan. [ABSTRACT FROM PUBLISHER]

Importance: 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., Objective: To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach., Design, Setting, and Participants: 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., Exposures: Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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 & Aims: Colorectal cancer (CRC) deaths occur when patients do not receive screening or have inadequate follow-up of abnormal results or when the screening test fails. We have few data on the contribution of each to CRC-associated deaths or factors associated with these events., Methods: We performed a retrospective cohort study of patients in the Kaiser Permanente Northern and Southern California systems (55-90 years old) who died of CRC from 2006 through 2012 and had ≥5 years of enrollment before diagnosis. We compared data from patients with those from a matched cohort of cancer-free patients in the same system. Receipt, results, indications, and follow-up of CRC tests in the 10-year period before diagnosis were obtained from electronic databases and chart audits., Results: Of 1750 CRC deaths, 75.9% (n = 1328) occurred in patients who were not up to date in screening and 24.1% (n = 422) occurred in patients who were up to date. Failure to screen was associated with fewer visits to primary care physicians. Of 3486 cancer-free patients, 44.6% were up to date in their screening. Patients who were up to date in their screening had a lower risk of CRC death (odds ratio, 0.38; 95% confidence interval, 0.33-0.44). Failure to screen, or failure to screen at appropriate intervals, occurred in a 67.8% of patients who died of CRC vs 53.2% of cancer-free patients; failure to follow-up on abnormal results occurred in 8.1% of patients who died of CRC vs 2.2% of cancer-free patients. CRC death was associated with higher odds of failure to screen or failure to screen at appropriate intervals (odds ratio, 2.40; 95% confidence interval, 2.07-2.77) and failure to follow-up on abnormal results (odds ratio, 7.26; 95% confidence interval, 5.26-10.03)., Conclusions: Being up to date on screening substantially decreases the risk of CRC death. In 2 health care systems with high rates of screening, most people who died of CRC had failures in the screening process that could be rectified, such as failure to follow-up on abnormal findings; these significantly increased the risk for CRC death., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Screening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers., Design: We conducted a nested case-control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55-90 years old on their colorectal cancer death date during 2006-2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures., Results: We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53)., Conclusions: Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Fecal immunochemical testing is the most commonly used method for colorectal cancer screening worldwide. However, its effectiveness is frequently undermined by failure to obtain follow-up colonoscopy after positive test results., Purpose: To evaluate interventions to improve rates of follow-up colonoscopy for adults after a positive result on a fecal test (guaiac or immunochemical)., Data Sources: English-language studies from the Cochrane Central Register of Controlled Trials, PubMed, and Embase from database inception through June 2017., Study Selection: Randomized and nonrandomized studies reporting an intervention for colonoscopy follow-up of asymptomatic adults with positive fecal test results., Data Extraction: Two reviewers independently extracted data and ranked study quality; 2 rated overall strength of evidence for each category of study type., Data Synthesis: Twenty-three studies were eligible for analysis, including 7 randomized and 16 nonrandomized studies. Three were at low risk of bias. Eleven studies described patient-level interventions (changes to invitation, provision of results or follow-up appointments, and patient navigators), 5 provider-level interventions (reminders or performance data), and 7 system-level interventions (automated referral, precolonoscopy telephone calls, patient registries, and quality improvement efforts). Moderate evidence supported patient navigators and provider reminders or performance data. Evidence for system-level interventions was low. Seventeen studies reported the proportion of test-positive patients who completed colonoscopy compared with a control population, with absolute differences of -7.4 percentage points (95% CI, -19 to 4.3 percentage points) to 25 percentage points (CI, 14 to 35 percentage points)., Limitation: More than half of studies were at high or very high risk of bias; heterogeneous study designs and characteristics precluded meta-analysis., Conclusion: Patient navigators and giving providers reminders or performance data may help improve colonoscopy rates of asymptomatic adults with positive fecal blood test results. Current evidence about useful system-level interventions is scant and insufficient., Primary Funding Source: National Cancer Institute. (PROSPERO: CRD42016048286).

Background: The Food and Drug Administration has issued a public health advisory regarding cancer risk from topical calcineurin inhibitors., Objective: To compare the rates of cancer among patients with common dermatologic conditions who were exposed or not exposed to topical calcineurin inhibitors., Methods: A retrospective cohort observational study used data from an integrated healthcare delivery system on 953,064 subjects with diagnoses of atopic dermatitis or eczema between 2001 and December 2004. The main endpoint was initial cancer diagnosis. Chart review was performed to confirm cancer diagnosis in the subjects exposed to topical calcineurin inhibitors when any particular cancer rate was at least 3 times higher than that in unexposed subjects. Data were analyzed using the Cox proportional hazards model., Results: Age- and sex-adjusted hazard ratios for all cancers were 0.93 (95% CI 0.81 to 1.07; p = 0.306) for tacrolimus-exposed versus -unexposed subjects and 1.15 (95% CI 0.99 to 1.31; p = 0.054) for pimecrolimus-exposed versus -unexposed subjects. T-cell lymphoma was the only cancer associated with a significantly increased risk among subjects exposed to tacrolimus (HR = 5.04, 95% CI 2.39 to 10.63; p < 0.001) or pimecrolimus (HR = 3.76, 95% CI 1.71 to 8.28; p = 0.010). Subsequent chart review of subjects in the exposed group with T-cell lymphoma found that 4 of 16 had skin lesions that were suspected to be the early lesions of T-cell lymphoma prior to exposure to tacrolimus or pimecrolimus. After these 4 cases were excluded, the age and sex hazard ratio for T-cell lymphoma was 5.44 (95% CI 2.51 to 11.79; p < 0.001) for tacrolimus and 2.32 (95% CI 0.89 to 6.07; p = 0.086) for pimecrolimus. There was no statistically significantly increased risk for other subgroups of cancer, including melanoma., Conclusions: Exposure to topical tacrolimus or pimecrolimus was not associated with an increase in the overall cancer rate. Use of topical tacrolimus may be associated with an increased risk of T-cell lymphoma.

The suitability of Ortho Diagnostics one-stage prothrombin time (PT) reagent (Ortho Brain Thromboplastin) and activated partial thromboplastin (aPTT) reagent (Activated Thrombofax) has been evaluated for use in conjunction with the anion-exchange heparin removal maneuver. The PT/HR and aPTT/HR are tests used to follow the anticoagulant influence of coumarins when heparin also is being administered. After establishing a coumarin therapeutic range for Activated Thrombofax, a parallel trial was conducted with Ortho Brain Thromboplastin on coumarin-treated patient plasmas. Determinations also were made after heparin (0.2 mu/mL) was added and then removed by ECTEOLA microchromatography columns. Ortho Brain Thromboplastin was found to induce a shortening bias associated with a spurious improvement in the precision of tests run on anion-exchange treated plasmas that potentially could result in coumarin overdosage. The systematic error did not appear to result either from protracted incubation or the activation of prekallikrein, high molecular weight kininogen, Factor XI or XII. This reagent was found to perform appropriately with plasma not exposed to ECTEOLA. Activated Thrombofax gave reliable and reproducible results before and after heparin removal. This aPTT reagent could be used in the aPTT/HR anticoagulant surveillance scheme.