Comparative Performance of Common Fecal Immunochemical Tests : A Cross-Sectional Study.

BACKGROUND: Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited. OBJECTIVE: To compare the performance characteristics of 5 commonly used FITs, using colonoscopy as the reference standard. DESIGN: Cross-sectional study. (ClinicalTrials.gov: NCT03264898). SETTING: Three U.S. academic medical centers and affiliated endoscopy units. PARTICIPANTS: Patients aged 50 to 85 years undergoing screening or surveillance colonoscopy. INTERVENTION: Participants completed 5 different FITs before their colonoscopy, including 4 qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, QuickVue iFOB) and 1 quantitative test (OC-Auto FIT, which was run at the manufacturer's threshold for positivity of >100 ng/mL). MEASUREMENTS: The primary outcome was test performance (sensitivity and specificity) for each of the 5 FITs for advanced colorectal neoplasia (ACN), defined as advanced polyps or CRC. Positivity rates, positive and negative predictive values, and rates of unevaluable tests were compared. Multivariable models were used to identify factors affecting sensitivity. RESULTS: A total of 3761 participants were enrolled, with a mean age of 62.1 years (SD, 7.8); 63.2% of participants were female, 5.7% were Black, 86.4% were White, and 28.7% were Hispanic. There were 320 participants with ACN (8.5%), including 9 with CRC (0.2%). The test positivity rate varied 4-fold (3.9% to 16.4%) across FITs. Rates of unevaluable FITs ranged from 0.2% to 2.5%. The sensitivity for ACN varied from 10.1% to 36.7%, and specificity varied from 85.5% to 96.6%. Differences in sensitivity between FITs were all statistically significantly different except between Hemosure iFOB and QuickVue iFOB, and specificity differences were all statistically significantly different from one another. In addition to FIT brand, distal location of ACN was also associated with higher FIT sensitivity. LIMITATION: The study did not assess the programmatic sensitivity of annual FIT. CONCLUSION: Although considered a single class, FITs have varying test performance for detecting ACN and should not be considered interchangeable. PRIMARY FUNDING SOURCE: National Institutes of Health.

Opportunities and challenges related to saturation of toxicokinetic processes: Implications for risk assessment.

Top dose selection for repeated dose animal studies has generally focused on identification of apical endpoints, use of the limit dose, or determination of a maximum tolerated dose (MTD). The intent is to optimize the ability of toxicity tests performed in a small number of animals to detect effects for hazard identification. An alternative approach, the kinetically derived maximum dose (KMD), has been proposed as a mechanism to integrate toxicokinetic (TK) data into the dose selection process. The approach refers to the dose above which the systemic exposures depart from being proportional to external doses. This non-linear external-internal dose relationship arises from saturation or limitation of TK process(es), such as absorption or metabolism. The importance of TK information is widely acknowledged when assessing human health risks arising from exposures to environmental chemicals, as TK determines the amount of chemical at potential sites of toxicological responses. However, there have been differing opinions and interpretations within the scientific and regulatory communities related to the validity and application of the KMD concept. A multi-stakeholder working group, led by the Health and Environmental Sciences Institute (HESI), was formed to provide an opportunity for impacted stakeholders to address commonly raised scientific and technical issues related to this topic and, more specifically, a weight of evidence approach is recommended to inform design and dose selection for repeated dose animal studies. Commonly raised challenges related to the use of TK data for dose selection are discussed, recommendations are provided, and illustrative case examples are provided to address these challenges or refute misconceptions.

Comparative effectiveness of five fecal immunochemical tests using colonoscopy as the gold standard: study protocol.

BACKGROUND: There are nearly 50,000 colorectal cancer (CRC) deaths in the United States each year. CRC is curable if detected in its early stages. Fecal immunochemical tests (FITs) can detect precursor lesions and many can be analyzed at the point-of-care (POC) in physician offices. However, there are few data to guide test selection. Broader use of FITs could make CRC screening more accessible, especially in resource-poor settings. METHODS: A total of 3600 racially and ethnically diverse individuals aged 50 to 85 years having either a screening or surveillance colonoscopy will be recruited. Each participant will complete five FITs on a single stool sample. Test characteristics for each FIT for advanced colorectal neoplasia (ACN) will be calculated using colonoscopy as the gold standard. RESULTS: We have complete data from a total of 2990 individuals. Thirty percent are Latino and 5.3% are black/African American. We will present full results once the study is completed. CONCLUSIONS: Our focus in this study is how well FITs detect ACN, using colonoscopy as the gold standard. Four of the five FITs being used are POC tests. Although FITs have been shown to have acceptable performance, there is little data to guide which ones have the best test characteristics and colonoscopy is the main CRC screening test used in the United States. Use of FITs will allow broader segments of the population to access CRC screening because these tests require no preparation, are inexpensive, and can be collected in the privacy of one's home. Increasing CRC screening uptake will reduce the burden of advanced adenomas and colorectal cancer.

Gas Exchange, Water Use Efficiency, and Biomass Partitioning among Geographic Sources of Acer saccharum Subsp. saccharum and Subsp. nigrum Seedlings in Response to Water Stress.

Responses to water stress were measured for sugar maple (Acer saccharum subsp. saccharum Marshall) sources from Oklahoma (Caddo sugar maple), Missouri, Tennessee, Ontario, and a black maple (Acer saccharum subsp. nigrum F. Michx.) source from Iowa. Seedling sources were selected for differences in temperature and precipitation of their geographic origins. Seedlings were preconditioned through moist (watered daily) or dry (watered every 4-7 days) cycles and then exposed to prolonged water stress. As water stress increased, dry preconditioned 17-week-old sugar maple seedlings from Oklahoma, Missouri, and Tennessee, sources from warmer, and/or drier climates with greater restrained photosynthesis, stomatal conductance, and water use efficiency than those from cooler and moister climates. Under imposed water stress, the Ontario and Iowa sourced seedlings increased their root to shoot ratios and decreased their specific leaf area, mechanisms for drought avoidance. However, no corresponding changes in these values occurred for Oklahoma, Missouri, and Tennessee sources and for the variable of leaf wilting across all sources. Results from this study suggest greater tolerance of water stress in the Oklahoma, Missouri, and Tennessee ecotypes from the western and southern range of sugar maple resulted primarily with water use efficiency (WUE) rather than other water stress coping mechanisms. Findings from this study provide evidence to support selection of sugar maples sources for forestation.

Intradural pathology and pathophysiology associated with Chiari I malformation in children and adults with and without syringomyelia.

OBJECTIVE The pathophysiology underlying tonsillar herniation and CSF obstruction in Chiari malformation Type I (CM-I) is unclear, and the cause of CM-I-associated syringomyelia is not well understood. A better understanding of this pathophysiology is important for an improved treatment strategy. Therefore, the authors sought to identify, characterize, and examine the intradural pathology and CSF flow pathophysiology in the posterior fossa and at the level of the foramen magnum that occurs in the setting of CM-I. They determined the incidence of these intradural findings and assessed differences across age, with the degree of tonsillar herniation, and in the presence and absence of syringomyelia. METHODS A prospective database initiated in March 2003 recorded all intraoperative findings during surgical treatment of children and adults with CM-I with or without syringomyelia. A total of 389 surgeries for CM-I were performed in 379 patients between March 2003 and June 2016. A total of 109 surgeries were performed in 109 patients with CM-I (without osseoligamentous abnormalities) in whom both a posterior fossa extradural and intradural decompression with duraplasty was performed (first-time intradural procedures). Using a surgical microscope, intradural pathology and obstruction of CSF channels were identified and assessed. Student t-tests and Fisher's exact tests compared groups in a series of univariate analyses, followed by multivariate logistic regression. RESULTS The following intradural pathological entities were observed (prevalence noted in parentheses). These include those that did not obstruct CSF flow channels: opacified arachnoid (33.0%), thickened arachnoid (3.7%), ischemic and gliotic tonsils (40.4%), tonsillar cysts (0.9%), and inferior descent of the fourth ventricle and cervicomedullary junction (CMJ) (78.0%). The following intradural pathological entities were observed to obstruct CSF flow channels: medialized tonsils (100%), tonsil overlying and obstructing the foramen of Magendie (21.1%), intertonsillar and tonsil to CMJ arachnoid adhesions (85.3%), vermian posterior inferior cerebellar artery branches obstructing the foramen of Magendie (43.1%), and arachnoid veils or webs obstructing or occluding the foramen of Magendie (52.3%). Arachnoid veils varied in type and were observed in 59.5% of patients with CM-I who had syringomyelia, which was significantly greater than the 33.3% of patients with CM-I without syringomyelia who had an arachnoid veil (p = 0.018). The presence of CM-I with an arachnoid veil had 3.22 times the odds (p = 0.013, 95% CI 1.29-8.07, by multivariate logistic regression) of being associated with syringomyelia, adjusting for tonsillar herniation. The inferior descent of the fourth ventricle and CMJ occurred with a greater degree of tonsillar herniation (p < 0.001) and correlated with a cervicomedullary kink or buckle on preoperative MRI. CONCLUSIONS Intradural pathology associated with CM-I with or without syringomyelia exists in many forms, is more prevalent than previously recognized in patients of all ages, and may play a role in the pathophysiology of CM-I tonsillar herniation. Arachnoid veils appear to partially obstruct CSF flow, are significantly more prevalent in cases of CM-I with syringomyelia, and therefore may play a role in the pathophysiology of CM-I-associated syringomyelia.

Promoting healthy choices in non-chain restaurants: effects of a simple cue to customers.

This study tested a novel intervention to influence restaurant customer ordering behavior, with measurements at baseline and 3, 6, and 12 months postintervention in four owner-operated restaurants in the Midwest. A sample of 141 to 370 customers was surveyed at each time point. The response rate was 70% to 84% with 59% women, 98% White, and a mean age of 53 years. Table signs listed changes customers might consider, for example, asking for meat broiled instead of fried or requesting smaller portions. Customer surveys measured program reach and effectiveness. Owner interviews measured perceptions of program burden and customer response. Order slips were analyzed for evidence of changes in ordering. Window signs were noticed by 40%, 48%, and 45% of customers at each follow-up, respectively. Table signs were noticed by 67%, 71%, and 69% of customers, respectively. Of those, 34% at each time point stated that the signs influenced their order. Examples of how orders were influenced were elicited. Order slip data not only did not show significant changes but was also found to be an inadequate measure for the intervention. Owners reported no concerns or complaints. This intervention resulted in small but positive behavior changes among a portion of customers. Because of its simplicity and acceptability, it has great potential for dissemination.

Elevated body mass index and risk of postoperative CSF leak following transsphenoidal surgery.

OBJECT: Postoperative CSF leakage can be a serious complication after a transsphenoidal surgical approach. An elevated body mass index (BMI) is a significant risk factor for spontaneous CSF leaks. However, there is no evidence correlating BMI with postoperative CSF leak after transsphenoidal surgery. The authors hypothesized that patients with elevated BMI would have a higher incidence of CSF leakage complications following transsphenoidal surgery. METHODS: The authors conducted a retrospective review of 121 patients who, between August 2005 and March 2010, underwent endoscopic endonasal transsphenoidal surgeries for resection of primarily sellar masses. Patients requiring extended transsphenoidal approaches were excluded. A multivariate statistical analysis was performed to investigate the association of BMI and other risk factors with postoperative CSF leakage. RESULTS: In 92 patients, 96 endonasal endoscopic transsphenoidal surgeries were performed that met inclusion criteria. Thirteen postoperative leaks occurred and required subsequent treatment, including lumbar drainage and/or reoperation. The average BMI of patients with a postoperative CSF leak was significantly greater than that in patients with no postoperative CSF leak (39.2 vs 32.9 kg/m(2), p = 0.006). Multivariate analyses indicate that for every 5-kg/m(2) increase in BMI, patients undergoing a transsphenoidal approach for a primarily sellar mass have 1.61 times the odds (95% CI 1.10-2.29, p = 0.016, by multivariate logistic regression) of having a postoperative CSF leak. CONCLUSIONS: Elevated BMI is an independent predictor of postoperative CSF leak after an endonasal endoscopic transsphenoidal approach. The authors recommend that patients with BMI greater than 30 kg/m(2) have meticulous sellar reconstruction at surgery and close monitoring postoperatively.

Barriers to the early cochlear implantation of deaf children.

OBJECTIVE: Identify social and health care system factors that prevent congenitally deaf children from receiving cochlear implants (CIs) in a timely fashion. STUDY DESIGN: Retrospective chart review and parental interviews. SETTING: University medical center hospital in a state with mandatory newborn hearing screening (NBHS). PATIENTS: Fifty-nine congenitally deaf children who received CIs between January 1, 2002, and May 1, 2009. INTERVENTIONS: Demographic and health care details were collected from the 59 patients. MAIN OUTCOME MEASURE: Age at implantation. RESULTS: Thirty-four patients received implants at or before age 2 years (average age at implant surgery, 14 mo), and 25 patients received implants after age 2 years (average age, 65 mo). The presence of NBHS (p<0.001) and type of health insurance (p=0.05) the child had at the time of CI surgery were significant predictors of age at implantation. The following factors were associated with increased risk of delayed implantation: no NBHS (risk ratio [RR]=2.63), NBHS not identifying hearing loss (RR=1.63), Medicaid insurance alone (RR=1.21) or in combination with private insurance (RR=1.79), family physician as primary care provider (RR=1.50), and audiologist (RR = 1.30) or otolaryngologist (RR=1.31) as secondary care providers (versus implant center, RR=0.23). The main reasons for delay in CI surgery after age 2 years also were identified and include slow referrals for care (n=8) and parental delays (n=5). CONCLUSION: The data suggest placing special focus on children with associated risk factors, ensuring NBHS, and parent and primary care provider education on the importance of early intervention and referral to an implant center would likely limit delays in children receiving CIs.

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.

Colorectal cancer testing among patients cared for by Iowa family physicians.

BACKGROUND: Colorectal cancer (CRC) can be largely prevented or effectively treated, yet about half of eligible Americans have not been screened. The purpose of this study was to examine patient and physician factors associated with documented CRC testing according to national guidelines. METHODS: Cross-sectional study where 511 randomly selected rural patients aged 55 to 80 years of 16 board-certified Iowa family physicians were enrolled in 2004. Patient survey and medical record information were linked with physician surveys. Predictors of CRC testing were examined using a regression procedure that accommodated random physician effects (2005-2006). RESULTS: Forty-six percent of patients were up-to-date with CRC testing in accordance with national guidelines. This percentage varied from 5% to 75% by physician (p < 0.0001). Of the patients who were up-to-date, 89% had colonoscopy, and 62% had symptoms prior to testing that could indicate CRC. The strongest univariate predictors other than symptoms were patient recollection of physician recommendation (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 4.2-9.6) and physician documentation of recommendation (OR = 14.1, CI = 8.5-23.3). A multivariable regression model showed testing in accordance with guidelines significantly increased with government insurance (OR = 1.6, CI = 1.2-2.3), having a health maintenance visit in the preceding 26 months (OR = 2.4, CI = 1.4-4.1), family history of CRC (OR = 3.1, CI = 1.6-5.8), number of medical conditions (OR = 1.2 for each additional condition, CI = 1.1-1.3), high importance of screening to patient (OR = 2.6, CI = 1.5-4.5), patient satisfaction with doctor's discussions (OR = 3.3, CI = 2.2-4.8), physician trained in flexible sigmoidoscopy (OR = 2.3, CI = 1.6-3.4), and physician report of trying to follow American Cancer Society (ACS) guidelines (OR = 1.7, CI = 1.2-2.5). After excluding patients who had symptoms prior to screening, most of the ORs in the logistic regression analysis increased except that the number of medical conditions and physician trying to follow ACS guidelines became nonsignificant. CONCLUSIONS: Fewer than half of rural patients received CRC testing, and most of those tested had symptoms. Physician recommendations and the manner of presenting the recommendations greatly influenced whether patients were tested.