Fecal Immunochemical Testing in Patients With Low-Risk Symptoms of Colorectal Cancer: A Diagnostic Accuracy Study.

BACKGROUND: The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. PATIENTS AND METHODS: Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 µg hemoglobin per gram of feces (µg/g). RESULTS: A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 µg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 µg/g, respectively. The sensitivity of FIT at ≥10 µg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. CONCLUSIONS: Utilization of FIT at a threshold ≥10 µg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.

Prenatal screening for Down syndrome in twin pregnancies: Estimates of screening performance based on 61 affected and 7302 unaffected twin pregnancies.

The aims of this study were to determine whether assumptions used in prenatal screening for Down syndrome in twin pregnancies are valid and derive estimates of risk and screening performance in twin pregnancies using observed data. Data were collected on nuchal translucency, chorionicity, pregnancy associated plasma protein-A (PAPP-A), and free ß human chorionic gonadotrophin (free ß-hCG) from 61 twin pregnancies with Down syndrome and 7302 unaffected twin pregnancies. Distribution parameters were determined and used to estimate screening performance. The assumption that proportional differences in serum marker levels in affected and unaffected singleton pregnancies apply to twin pregnancies was not confirmed. Median free ß-hCG value in monochorionic affected twin pregnancies (2.63 multiples of the median [MoM]; 95% CI, 1.79-3.22 MoM) was lower than that assuming proportionality (3.76 MoM), and the median PAPP-A value in dichorionic affected twin pregnancies (1.88 MoM; 95% CI, 1.60-2.17 MoM) was higher than that based on proportionality (1.33 MoM). The detection rate was 87% for a 3% false-positive rate in monochorionic twin pregnancies and 74% in dichorionic twin pregnancies compared with 86% in singleton pregnancies. Estimates of screening performance in Down syndrome twin pregnancies do not need to rely on assumptions and can take account of chorionicity and gestational age.

Down's syndrome screening: population statistic dependency of screening performance.

BACKGROUND: The choice of parameter sets used to calculate Down's syndrome risks is important. This study details analysis of samples from affected and unaffected pregnancies and evaluates whether published population data is optimal. Screening efficiency realized with measurement procedure-specific population parameters is compared with selected population sets available in the literature. METHODS: In a retrospective experiment, double and triple testing was performed on maternal serum samples from 286 randomly chosen unaffected singleton pregnancies and 95 Down's syndrome affected pregnancy samples. Using a risk cut-off of 1 in 250, detection rates and false positive rates were estimated for different population settings to select a model giving the best overall efficacy. Receiver operation characteristics curve analysis was performed and detection rates realized with the different population settings was estimated at a 5% fixed false positive rate. RESULTS: Geometric mean weight corrected multiples of the median values were 1.01 for alpha-fetoprotein (AFP), 1.02 for human chorionic gonadotropin (hCG) and 1.01 for unconjugated estriol (uE3) in unaffected pregnancies and 0.77 (95% CI: 0.71-0.83) for AFP, 2.42 (95% CI: 2.17-2.71) for hCG and 0.78 (95% CI: 0.73-0.83) for uE3 in affected pregnancies. Differences in double and triple risks obtained with the different models were significantly different from each other (p < 0.001). At a cut-off of 1 in 250, the maximum triple test detection rate was 75.8% for a false positive rate of 4.9% and was obtained with the measurement procedure-specific setting. At a fixed false positive rate of 5%, the maximum detection rate for the triple test was 77.9% (95% CI: 62.2%-85.8%). The maximum double test detection rate at 5% false positive rate was 69.6% (95% CI: 59.5%-78.5%). Except for two models, the area under the curve for the triple test was higher than that of the double test. CONCLUSIONS: The Access triple test meets the typical performance characteristics for this test combination. The assay-specific settings yielded the overall best efficacy for the criteria studied. Therefore, the availability of measurement procedure-specific mid-trimester reference values for unaffected and affected pregnancies in prenatal screening programs is essential. Such reference values are established for the Beckman Coulter Access triple test: maternal serum AFP, uE3 and hCG.