Splicing factor arginine/serine-rich 8 promotes multiple myeloma malignancy and bone lesion through alternative splicing of CACYBP and exosome-based cellular communication.

BACKGROUND: Multiple myeloma (MM) is a distinctive malignancy of plasma cell within the bone marrow (BM), of which alternative splicing factors play vital roles in the progression. Splicing factor arginine/serine-rich 8 (SFRS8) is the exclusive factor associated with MM prognosis, however its role in MM remains undefined. METHODS: The analyses of 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, immunohistochemistry, flow cytometry and xenograft model were performed to examine cell proliferation, cell cycle and apoptosis in SFRS8 overexpression or knockdown MM cells in vitro and in vivo. The SFRS8-regulated alternative splicing events were identified by RNA immunoprecipitation sequencing (RIP-seq) and validated by RIP-qPCR and Co-IP methods. Exosomes were extracted from the supernatant of myeloma cells by ultracentrifugation. Bone lesion was evaluated by TRAP staining in vitro and SCID/NOD-TIBIA mouse model. A neon electroporation system was utilised to deliver siRNA through exosomes. The effect of siRNA-loaded exosomes in vivo was evaluated by using a patient-derived tumor xenograft (PDX) model and SCID/NOD-TIBIA mouse model. RESULTS: SFRS8 was significantly upregulated in MM samples and positively associated with poor overall survival (OS) in MM patients. SFRS8 promoted MM cell proliferation in vitro and in vivo. Furthermore, calcyclin binding protein (CACYBP) was identified as the downstream target of SFRS8. Particularly, SFRS8 could reduce CACYBP isoform1 (NM_014412.3) and increase CACYBP isoform2 (NM_001007214.1) by mediating the alternative splicing of CACYBP, thereby altering the ubiquitination degradation of ß-catenin to promote MM progression. In addition, SFRS8 promoted osteoclast differentiation through exosomes in vitro and in vivo. More importantly, exosomal siRNA targeting CACYBP isoform2 inhibited tumour growth in PDX and SCID/NOD-TIBIA mouse models. CONCLUSION: Our findings demonstrate that targeting the SFRS8/CACYBP/ß-catenin axis may be a promising strategy for MM diagnosis and treatment.

A validation study of potential prognostic DNA methylation biomarkers in patients with acute myeloid leukemia using a custom DNA methylation sequencing panel.

BACKGROUND: Multiple studies have reported the prognostic impact of DNA methylation changes in acute myeloid leukemia (AML). However, these epigenetic markers have not been thoroughly validated and therefore are still not considered in clinical practice. Hence, we aimed to independently verify results of selected studies describing the relationship between DNA methylation of specific genes and their prognostic potential in predicting overall survival (OS) and event-free survival (EFS). RESULTS: Fourteen studies (published 2011-2019) comprising of 27 genes were subjected to validation by a custom NGS-based sequencing panel in 178 newly diagnosed non-M3 AML patients treated by 3 + 7 induction regimen. The results were considered as successfully validated, if both the log-rank test and multivariate Cox regression analysis had a p-value ≤ 0.05. The predictive role of DNA methylation was confirmed for three studies comprising of four genes: CEBPA (OS: p = 0.02; EFS: p = 0.03), PBX3 (EFS: p = 0.01), LZTS2 (OS: p = 0.05; EFS: p = 0.0003), and NR6A1 (OS: p = 0.004; EFS: p = 0.0003). For all of these genes, higher methylation was an indicator of longer survival. Concurrent higher methylation of both LZTS2 and NR6A1 was highly significant for survival in cytogenetically normal (CN) AML group (OS: p < 0.0001; EFS: p < 0.0001) as well as for the whole AML cohort (OS: p = 0.01; EFS < 0.0001). In contrast, for two studies reporting the poor prognostic effect of higher GPX3 and DLX4 methylation, we found the exact opposite, again linking higher GPX3 (OS: p = 0.006; EFS: p < 0.0001) and DLX4 (OS: p = 0.03; EFS = 0.03) methylation to a favorable treatment outcome. Individual gene significance levels refer to the outcomes of multivariate Cox regression analysis. CONCLUSIONS: Out of twenty-seven genes subjected to DNA methylation validation, a prognostic role was observed for six genes. Therefore, independent validation studies are necessary to reveal truly prognostic DNA methylation changes and to enable the introduction of these promising epigenetic markers into clinical practice.

Application of Behavioral Economics Principles Improves Participation in Mailed Outreach for Colorectal Cancer Screening.

INTRODUCTION: Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality in the United States. Although various interventions have improved screening rates, they often require abundant resources and can be difficult to implement. Social psychology and behavioral economics principles offer an opportunity for low-cost and easy-to-implement strategies but are less common in clinical settings. METHODS: We randomized 2,000 patients aged 50-75 years eligible for CRC screening to one of the 2 mailed interventions: a previously used text-based letter describing and offering fecal immunochemical testing (FIT) and colonoscopy (usual care arm); or a letter leveraging social psychology and behavioral economics principles (e.g., implied scarcity and choice architecture), minimal text, and multiple images to offer FIT and colonoscopy (intervention arm). We compared total screening uptake, FIT uptake, and colonoscopy uptake at 1-month intervals in each group. RESULTS: There were 1,882 patients included in the final analysis. The mean age was 69.3 years, and baseline characteristics in the 2 groups were similar. Screening completion at 26 weeks was 19.5% in the usual care arm (16.3% FIT vs 3.2% colonoscopy, P < 0.01) and 24.1% in the intervention arm (22.1% FIT vs 2.0% colonoscopy, P < 0.01) (P = 0.02). DISCUSSION: Among primary care patients aged 50-75 years in an academic setting, mailed CRC outreach employing social psychology and behavioral economics principles led to a higher participation in CRC screening than usual care mailed outreach. TRANSLATIONAL IMPACT: Mailed interventions to increase CRC screening should incorporate social psychology and behavioral economics principles to improve participation.

Faecal haemoglobin concentration among subjects with negative FIT results is associated with the detection rate of neoplasia at subsequent rounds: a prospective study in the context of population based screening programmes in Italy.

OBJECTIVE: To estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer-CRC-or advanced adenoma). DESIGN: Prospective cohort of subjects aged 50-69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy. METHODS: All programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method. RESULTS: The cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels. CONCLUSION: The association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb.

Longitudinal Adherence to Immunochemical Fecal Occult Blood Testing vs Guaiac-based FOBT in an Organized Colorectal Cancer Screening Program.

Longitudinal adherence is a critical component of the efficacy of stool-based screening programs because they should be repeated every 1-2 years. Few data have been published on the uptake in multiple rounds of fecal occult blood test-based (FOBT) colorectal cancer (CRC) screening. We calculated two measures of longitudinal adherence to biennial FOBT (guaiac fecal occult blood test:gFOBT or fecal immunochemical test:FIT) to better understand its impact on the programmatic effectiveness of a population-based CRC screening program (2000-2017). Ongoing population-based CRC program of men and women aged 50-69 years. Variables: Age at first CRC screening invitation, sex, number of screening invitations, number of screens, deprivation score, and uptake rate. Logistic regression models were used to assess the independent effect of sex, age at first invitation, deprivation, and the type of screening test offered on adherence. The uptake rate for guaiac fecal occult blood test (gFOBT) was 23.9%, and for the fecal immunochemical test (FIT), it was 37.4%. The overall rate of consistently screened invitees after seven rounds of screening was 14.2%, being 20.6% for those individuals who used FIT and 14.3% for those who used gFOBT. Factors associated with continued participation (consistent vs. inconsistent screenees) showed that the longitudinal adherence was associated with age, screening test used, and number of invitations. Continued participation was lower in individuals who were screened using FIT than among those screened using gFOBT [OR, 0.68; 95% confidence interval (CI), 0.57-0.81]. The overall rate of consistently screened invitees for colorectal cancer screening was higher with FIT than gFOBT. Studying the rate of individuals being current for screening may help to anticipate potential benefits before the long-term outcome data are available.

Quantitative immunochemical fecal occult blood test for neoplasia in colon cancer screening.

OBJECTIVE: To investigate the performance of the quantitative immunochemical fecal occult blood test (qFIT) and to determine the association between the fecal hemoglobin (Hb) level and the location and size of adenomas and the stages of colorectal cancer (CRC). METHODS: A total of 692 participants were included in the study. Their fecal Hb level was measured using an OC-SENSA MICRO qFIT. The colonoscopy results, including the location, size, and histological features of the adenomas, as well as the relationship between the Hb level and different characteristics were analyzed. Performance of the qFIT at various thresholds of fecal Hb levels was evaluated. RESULTS: Advanced colorectal neoplasia (ACRN) was identified in 76 patients based on the colonoscopic and pathological examinations. Large adenomas (≥10 mm) had a higher fecal Hb level than small adenomas (<10 mm). Advanced adenomas located on the left side of the colon presented with a higher fecal Hb level than those on the right side (P = 0.022). Stage III-IV CRC patients had a significantly higher Hb level than stage I-II patients (P = 0.013). The sensitivity and specificity of qFIT for ACRN was 51.3% and 86.4%，respectively, with the best cut-off level of 400 ng/mL. The sensitivity and specificity for CRC was 61.0% and 89.1%, with the best cut-off level of 500 ng/mL. CONCLUSIONS: qFIT has an acceptable sensitivity and specificity for ACRN detection. Furthermore, the qFIT results are associated with the location and size of adenomas as well as the grade of CRC.

Colorectal cancer screening in hospitalized patients: results from the Nationwide Inpatient Sample.

Colorectal cancer (CRC) is preventable with regular screening. This study aims to determine estimates and predictors of inpatient CRC screening during hospitalization in the USA. This nationwide population-based study utilized data from the National Inpatient Sample database from 2005 to 2014 to examine rates of CRC screening among hospitalized patients. There were 6470 inpatient CRC screening nationwide from 129 645 394 inpatient hospitalizations. Multivariable analysis showed that higher rates of inpatient CRC screening were associated with: females compared to males [odds ratio (OR): 0.87; 95% confidence interval (CI): 0.78-0.97]; 50-59 years age group compared to 70-79 years (OR: 0.76; 95% CI: 0.62-0.94) and more than 80 years (OR: 0.47; 95% CI: 0.35-0.64); Charlson Comorbidity Index score of 0 compared to scores of 1-2 (OR: 0.79; 95% CI: 0.64-0.98), 3-4 (OR: 0.61; 95% CI: 0.49-0.76), more than 5 (OR: 0.61; 95% CI: 0.47-0.79); rural hospitals rather than urban teaching hospital (OR: 0.50; 95% CI: 0.39-0.63) and urban nonteaching hospitals (OR: 0.64; 95% CI: 0.49-0.82); hospitals in the Midwest region (OR: 1.56; 95% CI: 1.14-2.12) compared to the Northeast region; recent years of 2011/2012 (OR: 1.89; 95% CI: 1.44-2.49) and 2013/2014 (OR: 2.70; 95% CI: 2.14-3.41) compared to the period 2005/2006. The CRC screening rate among hospitalized patients admitted in US hospitals is low. There were no association of differences in racial, household income or health insurance status with inpatient CRC screening. Noninvasive screening methods in hospitalized patients like stool-based fecal immunochemical test provide a unique method of increasing cancer screening rates.

A Multi-Level Fit-Based Quality Improvement Initiative to Improve Colorectal Cancer Screening in a Managed Care Population.

INTRODUCTION: Colorectal cancer (CRC) is a common but largely preventable disease with suboptimal screening rates despite national guidelines to screen individuals age 50-75. Single-component interventions aimed to improve screening uptake only modestly improve rates; data suggest that multi-modal approaches may be more effective. METHODS: We designed, implemented, and evaluated the impact of a multi-modal intervention on CRC screening uptake among unscreened patients in a large managed care population. Patient-level components included a mailed letter with education about screening options and pre-colonoscopy telephone counseling. For providers, we facilitated communication of screening test results and work-flow for abnormal results. System-level modifications included establishment of a patient navigator, expedited work-up for abnormal results, and stream-lined colonoscopy scheduling. We measured the rate of screening uptake overall, screening uptake by modality, change in the proportion of the population screened, and positive fecal immunochemical test (FIT) follow-up rates in the 1-year study period. RESULTS: There were 5093 patients in the intervention cohort. Of these, 33.2% participated in FIT or colonoscopy screening within 1 year of the mailing. A total of 1078 (21.2%) participants completed a FIT and 611 (12.0%) completed a screening colonoscopy. The screening rate in the managed care population increased from 65.1 to 76.6%. Fifty-nine patients (5.5%) had a positive FIT, of which 30 (50.8%) completed a diagnostic colonoscopy. CONCLUSION: Multi-modal interventions can result in substantial improvement in CRC screening uptake in large and diverse managed care populations. TRANSLATIONAL IMPACT: Health systems should shift their focus from single-level to multi-level interventions when addressing barriers to CRC screening.

Adherence to colorectal cancer screening measured as the proportion of time covered.

BACKGROUND AND AIMS: Colorectal cancer (CRC) screening can reduce CRC incidence and mortality, but measuring screening adherence over time is challenging. We examined adherence using a novel measure characterizing the proportion of time covered (PTC) by screening tests. METHODS: Eligible patients were age 50 to 60 years and followed at a large, safety-net health care system between January 2010 and September 2014. We estimated PTC as the number of days up to date with screening divided by the number of days from cohort entry until study end, CRC diagnosis, or death. We estimated mean and median PTC and used least-significant difference tests to assess differences in adherence by patient characteristics. RESULTS: Of 18,257 patients, most were non-Hispanic black (40.5%) or Hispanic (34.9%) and/or female (62.4%). Approximately 40% (n = 7559) were never screened during the study period; the remaining 10,698 patients completed 19,105 screening examinations (14,481 fecal immunochemical tests [FITs], 4393 colonoscopies, 94 sigmoidoscopies, and 137 barium enemas). Overall, the mean PTC was 29.1% (95% confidence interval [CI], 28.6%-29.5%). Among those who completed at least one screening test (n = 10,698), the mean PTC was 49.0% (95% CI, 48.5%-49.5%). The most common reasons for non-adherence were lack of repeat FIT and no diagnostic colonoscopy after abnormal results for the FIT. The mean PTC increased with the number of primary care visits (0 visits, 21%; 1 visit, 29%; 2-3 visits, 35%; ≥4 visits, 37%; all P < .05). CONCLUSIONS: PTC provides a reliable estimate of screening adherence, capturing breakdowns in the CRC screening process amenable to intervention. Repeat FIT and diagnostic colonoscopy are important intervention targets that may increase adherence in underserved populations.

Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue.

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.

Financial Incentives for Promoting Colorectal Cancer Screening: A Randomized, Comparative Effectiveness Trial.

OBJECTIVES: Offering financial incentives to promote or "nudge" participation in cancer screening programs, particularly among vulnerable populations who traditionally have lower rates of screening, has been suggested as a strategy to enhance screening uptake. However, effectiveness of such practices has not been established. Our aim was to determine whether offering small financial incentives would increase colorectal cancer (CRC) screening completion in a low-income, uninsured population. METHODS: We conducted a randomized, comparative effectiveness trial among primary care patients, aged 50-64 years, not up-to-date with CRC screening served by a large, safety net health system in Fort Worth, Texas. Patients were randomly assigned to mailed fecal immunochemical test (FIT) outreach (n=6,565), outreach plus a $5 incentive (n=1,000), or outreach plus a $10 incentive (n=1,000). Outreach included reminder phone calls and navigation to promote diagnostic colonoscopy completion for patients with abnormal FIT. Primary outcome was FIT completion within 1 year, assessed using an intent-to-screen analysis. RESULTS: FIT completion was 36.9% with vs. 36.2% without any financial incentive (P=0.60) and was also not statistically different for the $10 incentive (34.6%, P=0.32 vs. no incentive) or $5 incentive (39.2%, P=0.07 vs. no incentive) groups. Results did not differ substantially when stratified by age, sex, race/ethnicity, or neighborhood poverty rate. Median time to FIT return also did not differ across groups. CONCLUSIONS: Financial incentives, in the amount of $5 or $10 offered in exchange for responding to mailed invitation to complete FIT, do not impact CRC screening completion.

Importance of implementing an analytical quality control system in a core laboratory.

INTRODUCTION: The aim of the clinical laboratory is to provide useful information for screening, diagnosis and monitoring of disease. The laboratory should ensure the quality of extra-analytical and analytical process, based on set criteria. To do this, it develops and implements a system of internal quality control, designed to detect errors, and compare its data with other laboratories, through external quality control. In this way it has a tool to detect the fulfillment of the objectives set, and in case of errors, allowing corrective actions to be made, and ensure the reliability of the results. OBJECTIVE: This article sets out to describe the design and implementation of an internal quality control protocol, as well as its periodical assessment intervals (6 months) to determine compliance with pre-determined specifications (Stockholm Consensus(1)). MATERIALS AND METHODS: A total of 40 biochemical and 15 immunochemical methods were evaluated using three different control materials. Next, a standard operation procedure was planned to develop a system of internal quality control that included calculating the error of the analytical process, setting quality specifications, and verifying compliance. RESULTS: The quality control data were then statistically depicted as means, standard deviations, and coefficients of variation, as well as systematic, random, and total errors. The quality specifications were then fixed and the operational rules to apply in the analytical process were calculated. Finally, our data were compared with those of other laboratories through an external quality assurance program. DISCUSSION: The development of an analytical quality control system is a highly structured process. This should be designed to detect errors that compromise the stability of the analytical process. The laboratory should review its quality indicators, systematic, random and total error at regular intervals, in order to ensure that they are meeting pre-determined specifications, and if not, apply the appropriate corrective actions.

Difference in performance of fecal immunochemical tests with the same hemoglobin cutoff concentration in a nationwide colorectal cancer screening program.

BACKGROUND & AIMS: We investigated whether 2 quantitative fecal immunochemical tests (FITs) with the same cutoff concentration of fecal hemoglobin perform equivalently in identifying patients with colorectal cancer (CRC). METHODS: A total of 956,005 Taiwanese subjects, 50 to 69 years old, participated in a nationwide CRC screening program to compare results from 2 FITs; 78% were tested using the OC-Sensor (n = 747,076; Eiken Chemical Co, Tokyo, Japan) and 22% were tested using the HM-Jack (n = 208,929; Kyowa Medex Co Ltd, Tokyo, Japan), from 2004 through 2009. The cutoff concentration for a positive finding was 20 µg hemoglobin/g feces, based on a standardized reporting unit system. The tests were compared using short-term and long-term indicators of performance. RESULTS: The OC-Sensor test detected CRC in 0.21% of patients, with a positive predictive value of 6.8%. The HM-Jack test detected CRC in 0.17% of patients, with a positive predictive value of 5.2%. The rate of interval cancer rate was 30.7/100,000 person-years among subjects receiving the OC-Sensor test and 40.6/100,000 person-years among those receiving the HM-Jack test; there was significant difference in test sensitivity (80% vs 68%, P = .005) that was related to the detectability of proximal CRC. After adjusting for differences in city/county, age, sex, ambient temperature, and colonoscopy quality, significant differences were observed between the tests in the positive predictive value for cancer detection (adjusted relative risk = 1.29; 95% confidence interval, 1.14-1.46) and the rates of interval cancer (0.75; 95% confidence interval, 0.62-0.92). Although each test was estimated to reduce CRC mortality by approximately 10%, no significant difference in mortality was observed when the 2 groups were compared. CONCLUSIONS: Different brands of quantitative FITs, even with the same cutoff hemoglobin concentration, perform differently in mass screening. Population-level data should be gathered to verify the credibility of quantitative laboratory findings.

Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test.

OBJECTIVE: To compare the uptake of faecal immunochemical occult blood test (FIT) with guaiac faecal occult blood test (gFOBT) in a screening programme, with specific attention to the demographic and socioeconomic factors that might affect test uptake. SETTING: The Clalit Health Service screening programme, Israel. METHODS: Average-risk individuals aged 50-75 years were randomized into a FIT arm or gFOBT arm using a programme based on the socioeconomic status (SES) of their primary care clinics. G-FOBT was performed with Hemoccult SENSA™ (3 evacuations) and FIT with the OC- MICRO(TM) (3 evacuations, refrigerating mandated). The GLIMMIX model was used. RESULTS: There were 5,464 and 10,668 eligible participants in the FIT and gFOBT arms respectively. Compliance in taking the kits was better (but not statistically significantly better) with gFOBT (37.8% vs. 29.3%; odds ratio [OR] 1.43 [95% CI 0.73-2.80]; P = 0.227). Kit return was higher in the FIT arm (65.0% vs. 78.9%; OR 0.45 [95% CI 0.24-0.83], P = 0.021). Overall test uptake was affected by age, gender, being immigrant and SES (determined by whether or not the participant paid national insurance tax, and the SES of the primary care clinic). The overall uptake of gFOBT and FIT was comparable (OR 0.996 [95% CI 0.46-2.17], P = 0.99). CONCLUSIONS: Overall compliance for test uptake was comparable between the two methods despite the more demanding procedure in the FIT arm. Sociodemographic parameters were the major determinants of compliance. An educational programme, with emphasis on the sociodemographic characteristics of the target population, should be instigated.

Colorectal cancer screening adherence is higher with fecal immunochemical tests than guaiac-based fecal occult blood tests: a randomized, controlled trial.

OBJECTIVES: Determine whether colorectal cancer screening adherence is greater with fecal immunochemical tests (FIT) or guaiac-based fecal occult blood tests (gFOBT). METHODS: We used electronic health records to identify 3869 New Mexico Veterans Affairs Health Care System primary care patients due for screening in 2008 for whom fecal blood testing was appropriate. We invited randomly selected patients by mail to participate in a study comparing FIT and gFOBT. We randomly allocated 404 subjects to receive FIT (n=202) or gFOBT (n=202) by mail. We determined the proportion of subjects completing testing within 90days of agreeing to participate in the study. We also used multivariate logistic regression to evaluate screening completion, adjusting for age, gender, race/ethnicity, clinic site, previous gFOBT testing, and co-morbidity. RESULTS: Screening adherence was higher with FIT than gFOBT (61.4% vs. 50.5%, P=0.03). The adjusted odds ratio for completing FIT vs. gFOBT was 1.56, 95% CI 1.04, 2.32. CONCLUSION: In a clinic setting of patients who were due for colorectal cancer screening, adherence was significantly higher with FIT than gFOBT.

Utility of micral test strips in screening for microalbuminuria.

OBJECTIVE: To evaluate the clinical utility of Micral strips for detection of microalbuminuria. DESIGN: One hundred three urine samples were tested by Micral strips for the presence of microalbuminuria, and the results were compared with the immunonephelometric method. SETTING: Endocrine diabetes clinic in a university-affiliated outpatient facility and the associated clinical laboratory. PATIENTS: Sixty-seven, 24-hour urine samples were obtained from 64 patients with diabetes. Thirty-six urine samples were obtained from normal controls; 22 of these were 24-hour samples and 14 were overnight samples. MAIN OUTCOME MEASURE: Concordance of results obtained by the two methods for the presence or absence of microalbuminuria. RESULTS: All 36 control subjects and 44 urine samples from diabetic patients had normal albumin excretion (<15 mg/24 h) by the immunonephelometric method. Seventy-eight of these were correctly identified as negative by Micral strips, giving a specificity of 97.5%. There were 23 samples with albumin excretion of more than 16 mg/24 h. Sixteen of these were correctly identified, giving a sensitivity of 69.5%. There were 16 samples with albumin excretion of 30 mg/24 h or more; 14 of these were correctly identified by Micral strips, and two were false negatives, giving a sensitivity of 87.7%. However, when urine samples with albumin concentrations of less than 11 mg/L were excluded, the Micral strips correctly read 21 out of 23 samples, giving a sensitivity of 91.3%. CONCLUSIONS: The specificity of Micral strips for detection of albuminuria in 24-hour urine samples is high (97.5%), but the sensitivity is low, ranging from 69.5% to 87.7%. The sensitivity was greatly improved when urine samples with albumin concentrations of less than 11 mg/L were excluded.

Immunochemical detection using the light-addressable potentiometric sensor.

Rapid, sensitive and flexible assay systems are needed for immunoassays, receptor-ligand binding studies and DNA probe assays. Filtration capture and sensor detection offer several advantages to these areas. Although dependent on the affinity of the specific binders employed, the sensitivity of these techniques can be in the order of 10(-12) M, and total assay time can be less than 15 minutes.

[Evaluation of a new commercial kit for emergency determination of serum myoglobin]. / Evaluation d'une nouvelle trousse commerciale pour le dosage en urgence de la myoglobine sérique.

The usefulness of a nephelometric-based serum myoglobin assay kit in the early diagnosis of acute myocardial infarction was assessed in 92 consecutive patients admitted within 24 hours of the onset of spontaneous chest pain lasting > or = 20 minutes. The discharge diagnosis was acute myocardial infarction in 37 patients (40.2%), myocardial infarction lasting > or = 6 hours in 10, and no myocardial infarction in 45 (48.9%). The characteristic curve showed that the best differential diagnostic value was a serum myoglobin > or = 130 micrograms/l (sensitivity, 75.6%; specificity, 91.7%; positive-predictive value, 88%; negative-predictive value, 82%). The initial diagnosis was doubtful in 33 patients (36%) because of an inconclusive electrocardiogram. A serum myoglobin value of > or = 130 micrograms/l would have identified 9 of the 13 patients with acute myocardial infarction and all of the 20 patients without myocardial infarction, giving an accuracy of 84.8%. These results suggest that this new rapid, quantitative serum myoglobin assay would be useful in the evaluation of suspected myocardial infarction, especially in patients with an inconclusive electrocardiogram.

Influence of biological variations and sample handling on measured microalbuminuria in diabetic patients.

Five immunochemical assays for determining low concentrations of albumin were investigated. These were a radioimmunoassay (RIA); turbidimetric immunoassays (TIA) both according to end-point measuring principle on a Cobas Fara and Hitachi 717 analysers, and according to kinetic measuring principle on a Turbitimer instrument; and a nephelometric immunoassay (NIA). All achieved the analytical goal necessary for optimal patient care. The correlations between the albumin concentrations measured with the different techniques were very good. In vitro glycation of albumin did not influence albumin concentrations measured by the five assays. Urine albumin excretion measured over 3 consecutive days showed considerable day-to-day variation. This was highest for spot-urine specimens and significantly lower for 24 h and timed-overnight samples. Variation of storage temperature (room temperature, 4 degrees C, -20 degrees C), time (up till 3 months), and pH (within the range pH 5-8) of the urine samples did not change significantly the measured albumin concentrations. Different sample preparations (vortex-mixing, centrifugation, and thawing) had no influence on the measured albumin concentration. In conclusion, a maximum standardization of the collection of timed-overnight urine samples for screening and 24 h urine samples for confirmation of microalbuminuria during 3 consecutive days is more crucial than the choice of the immunological technique.