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Traditional serrated adenomas (TSAs) may confer increased risk for colorectal cancer (CRC). Our objective with this study was to examine clinical characteristics and long-term outcomes associated with TSA diagnosis.We conducted a retrospective cohort study of U.S. Veterans ≥18 years of age with ≥1 TSA between 1999 and 2016. Baseline characteristics, colonoscopy findings, and diagnosis of incident and fatal CRC were abstracted. Advanced neoplasia was defined by CRC or adenoma with high-grade dysplasia, villous histology, or size ≥1 cm. Follow-up was through CRC diagnosis, death, or end of study (December 31, 2018).A total of 853 Veterans with a baseline TSA were identified; 74% were ≥60 years of age, 96% were men, 14% were Black, and 73% were non-Hispanic White. About 64% were current or former smokers. Over 2044 total person-years at follow-up, there were 11 incident CRC cases and 1 CRC death. Cumulative CRC incidence was 1.34% (95% confidence interval [CI], 0.67%-2.68%), and cumulative CRC death was 0.12% (95% CI, 0.00%-0.35%). Among the subset of 378 TSA patients with ≥1 surveillance colonoscopy, 65.1% had high-risk neoplasia on follow-up. CRC incidence among TSA patients was significantly higher than in a comparison cohort of patients with normal baseline colonoscopy at baseline (hazard ratio, 3.70; 95% CI, 1.63-8.41) and similar to a comparison cohort with baseline conventional advanced adenoma (hazard ratio, 0.86; 95% CI, 0.45-1.64).Individuals with TSA have substantial risk for CRC, based on their cumulative CRC incidence, as well as significant risk of developing other high-risk neoplasia at follow-up surveillance colonoscopy. These data underscore importance of current recommendations for close colonoscopy surveillance after TSA diagnosis.

Introduction: Retinopathy of prematurity (ROP) is a multifactorial disease and a preventable cause of blindness in childhood. Hyperoxia and hypoxia can cause retinal neovascularization resulting in retinal detachment and blindness if left untreated. Besides oxygen treatment, other reasons for ROP development are well known. We prospectively adopt various strategies to keep oxygen saturation (SpO2) within targets, between 91 and 95% for those on supplemental oxygen. By adapting this, we postulated that the incidence of severe ROP might be reduced. Methods: 2018–2019 provided pre-intervention and 2020 post-intervention data for the project. For all babies (≤32 weeks, ≤1,500 g with FiO2 >0.21), target SpO2 between 91 and 95% was measured as a percentage of time spent within and outside target SpO2 during 1–4 weeks of life. Results: 112 and 60 preterm neonates were screened for ROP during the pre- and post-intervention phase. Twenty neonates (18.3%) during pre-intervention and 16 (26.7%) in the post-intervention phase developed severe ROP requiring treatment. Despite a statistically significant increase of 10 percent points in time spent within target SpO2 (91–95%) in the post-intervention phase (p < 0.05), the incidence of severe ROP did not decline. Using a multivariate model, odds of ROP development decreased with gestational age (25%) while increasing with PDA requiring treatment (4.33 times) and glucose ≥10 mg/dL (4.15 times), considering one variable at a time, keeping others constant. Conclusion: Our QI project showed successful attainment of maximum time; the SpO2 remained within targets during supplemental oxygen; however, the incidence of severe ROP had not declined. Factors other than SpO2 might be responsible for a high incidence of ROP in our neonatal intensive care unit.

Primary open-angle glaucoma (POAG) is a degenerative eye disease for which early treatment is critical to mitigate visual impairment and irreversible blindness. POAG-associated loci individually confer incremental risk. Genetic risk score(s) (GRS) could enable POAG risk stratification. Despite significantly higher POAG burden among individuals of African ancestry (AFR), GRS are limited in this population. A recent large-scale, multi-ancestry meta-analysis identified 127 POAG-associated loci and calculated cross-ancestry and ancestry-specific effect estimates, including in European ancestry (EUR) and AFR individuals. We assessed the utility of the 127-variant GRS for POAG risk stratification in EUR and AFR Veterans in the Million Veteran Program (MVP). We also explored the association between GRS and documented invasive glaucoma surgery (IGS).Cross-sectional study.MVP Veterans with imputed genetic data, including 5830 POAG cases (445 with IGS documented in the electronic health record) and 64 476 controls.We tested unweighted and weighted GRS of 127 published risk variants in EUR (3382 cases and 58 811 controls) and AFR (2448 cases and 5665 controls) Veterans in the MVP. Weighted GRS were calculated using effect estimates from the most recently published report of cross-ancestry and ancestry-specific meta-analyses. We also evaluated GRS in POAG cases with documented IGS.Performance of 127-variant GRS in EUR and AFR Veterans for POAG risk stratification and association with documented IGS.GRS were significantly associated with POAG (Plt; 5 × 10sup-5/sup) in both groups; a higher proportion of EUR compared with AFR were consistently categorized in the top GRS decile (21.9%-23.6% and 12.9%-14.5%, respectively). Only GRS weighted by ancestry-specific effect estimates were associated with IGS documentation in AFR cases; all GRS types were associated with IGS in EUR cases.Varied performance of the GRS for POAG risk stratification and documented IGS association in EUR and AFR Veterans highlights (1) the complex risk architecture of POAG, (2) the importance of diverse representation in genomics studies that inform GRS construction and evaluation, and (3) the necessity of expanding diverse POAG-related genomic data so that GRS can equitably aid in screening individuals at high risk of POAG and who may require more aggressive treatment.

Delays in colonoscopy work-up for red flag signs or symptoms of colorectal cancer (CRC) during the COVID-19 pandemic are not well characterized. To examine colonoscopy uptake and time to colonoscopy after red flag diagnosis, before and during the COVID-19 pandemic. Cohort study of adults ages 50-75 with iron deficiency anemia (IDA), hematochezia, or abnormal stool blood test receiving Veterans Health Administration (VHA) care from April 2019 to December 2020. Index date was first red flag diagnosis date, categorized into "pre" (April-December 2019) and "intra" (April-December 2020) policy implementation prioritizing diagnostic procedures, allowing for a 3-month "washout" (January-March 2020) period. Outcomes were colonoscopy completion and time to colonoscopy pre- vs. intra-COVID-19, examined using multivariable Cox models with hazard ratios (aHRs) and 95% confidence intervals (CIs). There were 52,539 adults with red flag signs or symptoms (pre-COVID: 25,154; washout: 7527; intra-COVID: 19,858). Proportion completing colonoscopy was similar pre- vs. intra-COVID-19 (27.0% vs. 26.5%; p = 0.24). Median time to colonoscopy among colonoscopy completers was similar for pre- vs. intra-COVID-19 (46 vs. 42days), but longer for individuals with IDA (60 vs. 49days). There was no association between time period and colonoscopy completion (aHR: 0.99, 95% CI 0.95-1.03). Colonoscopy work-up of CRC red flag signs and symptoms was not delayed within VHA during the COVID-19 pandemic, possibly due to VHA policies supporting prioritization and completion. Further work is needed to understand how COVID-19 policies on screening and surveillance impact CRC-related outcomes, and how to optimize colonoscopy completion after a red flag diagnosis.

Ventricular dysfunction may be found in 40% of newborns with CDH, and is not only a predictor of disease severity, but also mortality and need for ECMO. We conducted this study to assess the utility of serial echocardiography in management of newborns with CDH and their survival outcomes. This is a retrospective study, wherein the demographic, clinical and echocardiographic data from our local CDH registry and hospital clinical database were analyzed to study the correlation of timed echocardiographic findings with mortality and other outcomes. Fourty-two newborns with CDH were admitted during the study period (M/F:19/23), with median gestation of 38 weeks (IQR:36–39) and birth weight of 2.83 kg (IQR 2.45–3.17). Thirty-one were left-sided, seven right, one central, and three bilateral hernias. Twelve infants (28%) died in early infancy. Three infants were excluded from analysis due to either palliation at birth or significant cardiac anomaly. A total of 137 echos from 39 infants were analyzed. Seventy percent of newborns who died and had an echo within the first 72 h, were noted to have suffered from moderate to severe PH. Birth weight < 2.8 kg, RVSP > 45.5 in the first 72 h and postoperative VIS > 23.5 and RSS > 4.3 were good predictors of mortality. Markers of elevated pulmonary pressures and cardiac function were useful in guiding therapy. Serial timed functional echocardiography (f-Echo) monitoring allows targeted therapy of patients with CDH. Birth weight, initial severity of pulmonary hypertension and postoperative RSS and VIS may be useful in predicting mortality.Other Information Published in: Pediatric Cardiology License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s00246-022-03002-y

Colorectal cancer (CRC) is the second-leading cause of cancer death in the United States. Screening reduces CRC incidence and mortality. 2021 US Preventive Service Task Force (USPSTF) guidelines and available evidence support routine screening from ages 45 to 75, and individualized consideration of screening ages 76 to 85. USPSTF guidelines recommend annual guaiac fecal occult blood testing, annual fecal immunochemical testing (FIT), annual to every 3-year multitarget stool DNA-FIT, every 5-year sigmoidoscopy, every 10-year sigmoidoscopy with annual FIT, every 5-year computed tomographic colonography, and every 10-year colonoscopy as options for screening. The "best test is the one that gets done."

Inflammation is a cancer hallmark. NSAIDs improve overall survival (OS) in certain cancers. Real-world studies explored here whether NSAIDs improve non–small cell lung cancer (NSCLC) OS. Analyses independently interrogated clinical databases from The University of Texas MD Anderson Cancer Center (MDACC cohort, 1987 to 2015; 33,162 NSCLCs and 3,033 NSAID users) and Georgetown-MedStar health system (Georgetown cohort, 2000 to 2019; 4,497 NSCLCs and 1,993 NSAID users). Structured and unstructured clinical data were extracted from electronic health records using natural language processing (NLP). Associations were made between NSAID use and NSCLC prognostic features (tobacco use, gender, race, and body mass index, BMI). NSAIDs were statistically significantly (P < 0.0001) associated with increased NSCLC survival (5-year OS 29.7% for NSAID users vs. 13.1% for nonusers) in the MDACC cohort. NSAID users gained 11.6 months over nonusers in 5-year restricted mean survival time. Stratified analysis by stage, histopathology, and multicovariable assessment substantiated benefits. NSAID users were pooled independent of NSAID type and by NSAID type. Landmark analysis excluded immortal time bias. Survival improvements (P < 0.0001) were confirmed in the Georgetown cohort. Thus, real-world NSAID usage was independently associated with increased NSCLC survival in the MDACC and Georgetown cohorts. Findings were confirmed by landmark analyses and NSAID type. The OS benefits persisted despite tobacco use and did not depend on gender, race, or BMI (MDACC cohort, P < 0.0001). These real-world findings could guide future NSAID lung cancer randomized trials. Significance: NLP and real-world studies conducted in large cohorts explored whether NSAIDs improved survival across NSCLC stages, histopathology, gender, smoking history, or demographic groups. A statistically significant association between NSAID use and NSCLC survival was found. This provides a rationale for future NSAID randomized NSCLC trials.

Introduction: Chemoradiotherapy (CRT) with concurrent cisplatin-based chemotherapy is the treatment of choice of locally advanced head and neck cancers (LAHNC), but the optimal regimen of cisplatin remains contentious. Though 3-weekly cisplatin is the recommended schedule, it is associated with severe adverse reactions. A lower dose weekly schedule is generally accepted to be more tolerable and is widely used in our country. Methodology: Our study retrospectively compares the 3-weekly and the weekly concurrent cisplatin schedules in patients of LAHNC treated with CRT. Patients were selected for either schedule based on the treating physician’s preference. The two schedules were compared for treatment-related toxicities, radiotherapy interruptions, cumulative cisplatin doses delivered and overall survival (OS) as well as disease-free survival (DFS) at 2 years. Results: In our study, 43 patients received the 3-weekly schedule while 40 received the weekly schedule. Age, gender, disease stage or site did not affect selection for either regimen, except cancers of the nasopharynx and salivary glands, who almost exclusively received the 3-weekly schedule (90.1%). Patients who received adjuvant CRT after radical surgery were more likely to receive the weekly schedule (66.7%) while patients treated with up-front CRT were more often given the 3-weekly schedule (57.6%). Overall, the 3-weekly arm was associated with more toxicities and treatment breaks, but was more successful in delivering an adequate cumulative dose of cisplatin and had a better OS and DFS at 2 years follow up compared to the weekly arm. It also appeared that treating physicians were more likely to withhold one or more of the weekly cycles to manage treatment toxicity which lead to inadequate cumulative dosing in a high (45%) percentage of patients. Conclusion: Our study reiterates that the 3-weekly cisplatin arm has a better outcome profile than the weekly cisplatin arm at the price of increased toxicity. Weekly schedules have lower toxicities but may not achieve outcomes equivalent to 3-weekly unless adequate cumulative doses are achieved. As our study is retrospective and non-randomized, selection bias may have affected our results.

Background Although guidelines have long recommended objective pulmonary function testing to diagnose asthma and chronic obstructive lung disease (COPD), many primary care patients receive a clinical diagnosis of asthma or COPD without objective testing. This often leads to unnecessary treatment with associated incremental costs and side-effects, and delays actual diagnosis. Research Question What are the barriers and enablers to lung function testing for asthma and/or COPD in primary care? Study Design and Methods We searched the literature for qualitative and quantitative studies reporting barriers and/or enablers to in-office or out-of-office lung function testing for diagnosing asthma and/or COPD, in primary care. Two reviewers independently screened abstracts and full texts; assessed methodological quality using the Mixed Methods Appraisal Tool; and extracted data from included studies. Identified barriers and enablers were categorized using the Theoretical Domains Framework (TDF), applying a pre-established coding manual. Results We identified 7988 unique articles, reviewed 336 full-text articles, and included 18 studies in this systematic review. Of these 18, 12 were quantitative, 3 were qualitative, and 3 used mixed methods. All 18 addressed in-office testing and 11 also addressed out-of-office testing. Barriers and enablers overlapped for asthma and COPD, and in- and out-of-office settings. We identified more reported barriers (e.g. lack of knowledge of the usefulness of spirometry) than enablers (e.g. skills for performing reliable spirometry). Barriers mapped to 9 (of a possible 14) TDF domains (for both in- and out-of-office settings). Enablers mapped to three domains for in-office testing and five domains for out-of-office testing. Interpretation Barriers to objective testing for airways disease in primary care are complex and span many theoretical domains. Correspondingly, a successful intervention must leverage multiple behaviour change techniques. A theory-based, multifaceted intervention to address underuse of diagnostic testing for asthma or COPD should now be developed and tested.

Lynch syndrome (LS) is an autosomal dominant familial condition caused by a pathogenic variant (PV) in a DNA mismatch repair gene, which then predisposes carriers to various cancers.To review the pathogenesis, clinical presentation, differential diagnosis and clinical strategies for detection and management of LS.A narrative review synthesising knowledge from published literature, as well as current National Comprehensive Cancer Network guidelines for management of LS was conducted.LS tumours are characterised by unique pathogenesis, ultimately resulting in hypermutation, microsatellite instability and high immunogenicity that has significant implications for cancer risk, clinical presentation, treatment and surveillance. LS is one of the most common hereditary causes of cancer, and about 1 in 279 individuals carry a PV in an LS gene that predisposes to associated cancers. Individuals with LS have increased risks for colorectal, endometrial and other cancers, with significant variation in lifetime risk by LS-associated gene.As genetic testing becomes more widespread, the number of individuals identified with LS is expected to increase in the population. Understanding the pathogenesis of LS informs current strategies for detection and clinical management, and also guides future areas for clinical innovation. Unravelling the mechanisms by which these tumours evolve may help to more precisely tailor management by the gene involved.

Background Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD. Research question Does pre-exercise exposure to TRAP (DE300, PM2.5=300 μg/m3) have greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild-to-moderate COPD compared to former smokers with normal spirometry and healthy controls? Study design and Methods In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy never-smokers, 9 ex-smokers without COPD and 9 ex-smokers with COPD were separately exposed to filtered air (FA) and DE300 for 2 hours separated by a minimum of 4 weeks. Participants performed symptom limited constant load cycling tests within 2.5 hours of exposure with detailed cardiorespiratory and exertional symptom measurements. Results There was a significant negative effect of TRAP on exercise endurance time in healthy controls (DE300 vs. FA: 10.2±8.2 vs. 12.9±9.5 min, respectively; p=0.03), but not in ex-smokers without COPD (10.1±6.9 vs. 12.2±8.0 min; respectively, p=0.57) or ex-smokers with COPD (9.8±6.4 vs. 8.4±6.6 min, respectively, p=0.31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy controls. Interpretation Contrary to our hypothesis, it was the healthy controls rather than the ex-smokers with and without COPD that were negatively impacted by TRAP during exercise.

Background Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise. Methods We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2 or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis. Results Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend Conclusions Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.

Supplementary Table 6: The MD Anderson cohort 5-year survival rate and difference of 5-year restricted mean survival time in months between NSAID users and non-users by gender, race, and smoking status corresponding to Figure 2. Comparisons are made to the Georgetown cohort.

Supplemental Figure 2. The Kaplan-Meier analysis of overall survival and NSAID use in lung cancer cases within the MedStar-Georgetown University database (Georgetown cohort).

Supplemental Table 1. Nonsteroidal anti-inflammatory drugs analyzed by Natural Language Processing (NLP).

Supplemental Figure 4. Landmark analysis of the MedStar-Georgetown University Hospital Database (Georgetown cohort).

Supplementary Table 5: The MD Anderson and Georgetown cohorts 5-year survival rates and differences of 5-year restricted mean survival time in months between NSAID users and non-users for all patients and by stage and histopathology corresponding to Figure 1. The abbreviations are AD (adenocarcinoma) and SCC (squamous cell cancer), respectively.

Supplemental Table 2. Lung cancer patient characteristics in the MedStar-Georgetown University cohort. All lung cancers and those with adenocarcinoma (AD) or squamous cell cancer (SCC) histopathology are shown.

Supplemental Figure 5. The Kaplan-Meier analysis of overall lung cancer survival by NSAID type in (A) the MD Anderson Cancer Center database (MD Anderson cohort) and (B) the Georgetown cohort. Patients who used multiple NSAID types were excluded from this analysis.

Supplemental Table 3. Multicovariable Cox proportional hazards model with variables associated with overall survival for the MD Anderson Cancer Center cohort.

Supplemental Figure 1 displays the studied cohorts at MD Anderson Cancer Center (MD Anderson cohort) and the MedStar-Georgetown University Hospital (Georgetown cohort).

Supplemental Figure 3. Landmark analysis of the MD Anderson Cancer Center lung cancer cases.

Supplemental Table 4. Multicovariable analysis with variables associated with overall survival for the Georgetown cohort.

Inflammation is a cancer hallmark. NSAIDs improve overall survival (OS) in certain cancers. Real-world studies explored here whether NSAIDs improve non–small cell lung cancer (NSCLC) OS. Analyses independently interrogated clinical databases from The University of Texas MD Anderson Cancer Center (MDACC cohort, 1987 to 2015; 33,162 NSCLCs and 3,033 NSAID users) and Georgetown-MedStar health system (Georgetown cohort, 2000 to 2019; 4,497 NSCLCs and 1,993 NSAID users). Structured and unstructured clinical data were extracted from electronic health records using natural language processing (NLP). Associations were made between NSAID use and NSCLC prognostic features (tobacco use, gender, race, and body mass index, BMI). NSAIDs were statistically significantly (P < 0.0001) associated with increased NSCLC survival (5-year OS 29.7% for NSAID users vs. 13.1% for nonusers) in the MDACC cohort. NSAID users gained 11.6 months over nonusers in 5-year restricted mean survival time. Stratified analysis by stage, histopathology, and multicovariable assessment substantiated benefits. NSAID users were pooled independent of NSAID type and by NSAID type. Landmark analysis excluded immortal time bias. Survival improvements (P < 0.0001) were confirmed in the Georgetown cohort. Thus, real-world NSAID usage was independently associated with increased NSCLC survival in the MDACC and Georgetown cohorts. Findings were confirmed by landmark analyses and NSAID type. The OS benefits persisted despite tobacco use and did not depend on gender, race, or BMI (MDACC cohort, P < 0.0001). These real-world findings could guide future NSAID lung cancer randomized trials.Significance:NLP and real-world studies conducted in large cohorts explored whether NSAIDs improved survival across NSCLC stages, histopathology, gender, smoking history, or demographic groups. A statistically significant association between NSAID use and NSCLC survival was found. This provides a rationale for future NSAID randomized NSCLC trials.

DOC file, 30K, Definitions for Categories of Process Failures.

PDF file, 64K, Study Population.

Supplementary Appendix 3 from Screening for Colorectal Cancer in a Safety-Net Health Care System: Access to Care Is Critical and Has Implications for Screening Policy

Supplementary Appendix 2 from Screening for Colorectal Cancer in a Safety-Net Health Care System: Access to Care Is Critical and Has Implications for Screening Policy

PDF file - 83K, Statistical details regarding specification of cross-classified logistic models.

Background: Data on the number of individuals eligible for screening, and rates of screening, are necessary to assess national colorectal cancer screening efforts. Such data are sparse for safety-net health systems.Methods: A retrospective cohort study of individuals ages 50 to 75 served by a safety-net health system in Tarrant County, TX was conducted to determine (a) the size of the potential screen-eligible population ages 50 to 75, (b) the rate of screening over 5 years among individuals ages 54 to 75, and (c) the potential predictors of screening, including sex, race/ethnicity, insurance status, frequency of outpatient visits, and socioeconomic status.Results: Of 28,708 potential screen-eligible individuals, 20,416 were ages 54 to 75 and analyzed for screening; 22.0% were screened within the preceding 5 years. Female gender, Hispanic ethnicity, ages 65 to 75, insurance status, and two or more outpatient visits were independently associated with screening. Access to care was an important factor: adjusted odds ratio, 2.57 (95% confidence interval, 2.23-2.98) for any insurance; adjusted odds ratio, 3.53 (95% confidence interval, 3.15-3.97) for two or more outpatient visits.Conclusions: The screen-eligible population served by our safety-net health system was large, and the projected deficit in screen rates was substantial. Access to care was the dominant predictor of screening participation. If our results are replicable in similar health systems, the data suggest that screening guidelines and policy efforts must take into account the feasibility of proposed interventions. Strong advocacy for more resources for colorectal cancer screening interventions (including research into the best manner to provide screening for large populations) is needed. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2373–9)

Supplementary Appendix 1 from Screening for Colorectal Cancer in a Safety-Net Health Care System: Access to Care Is Critical and Has Implications for Screening Policy

Background: We (i) described variability in colorectal cancer (CRC) test use across multiple levels, including physician, clinic, and neighborhood; and (ii) compared the performance of novel cross-classified models versus traditional hierarchical models.Methods: We examined multilevel variation in CRC test use among patients not up-to-date with screening in a large, urban safety net health system (2011–2012). Outcomes included: (i) fecal occult blood test (FOBT) or (ii) colonoscopy and were ascertained using claims data during a 1-year follow-up. We compared Bayesian (i) cross-classified four-level logistic models nesting patients within separate, nonoverlapping “levels” (physicians, clinics, and census tracts) versus (ii) three hierarchical two-level models using deviance information criterion. Models were adjusted for covariates (patient sociodemographic factors, driving time to clinic, and census tract poverty rate).Results: Of 3,195 patients, 157 (4.9%) completed FOBT and 292 (9.1%) completed colonoscopy during the study year. Patients attended 19 clinics, saw 177 physicians, and resided in 332 census tracts. Significant variability was observed across all levels in both hierarchical and cross-classified models that was unexplained by measured covariates. For colonoscopy, variance was similar across all levels. For FOBT, physicians, followed by clinics, demonstrated the largest variability. Model fit using cross-classified models was superior or similar to 2-level hierarchical models.Conclusions: Significant and substantial variability was observed across neighborhood, physician, and clinic levels in CRC test use, suggesting the importance of factors at each of these levels on CRC testing.Impact: Future multilevel research and intervention should consider the simultaneous influences of multiple levels, including clinic, physician, and neighborhood. Cancer Epidemiol Biomarkers Prev; 23(7); 1346–55. ©2014 AACR.

Supplementary Information from Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

BACKGROUND & AIMS There is a lack of convenient, sensitive, non-invasive strategies for screening and surveillance for colorectal neoplasia. An assay combining the results of circulating gastrointestinal epithelial cells (CEC) and somatic mutations of cell-free DNA adjusting for age/sex using a unique algorithm is evaluated in patients requiring colonoscopy. METHODS A prospective single-site 458-subject study (asymptomatic: 43% screening/43% surveillance, enriched with 65 symptomatic subjects) undergoing colonoscopy was conducted. The test analyzed CEC and somatic mutations. The probability of advanced neoplasia (advanced adenoma (AA) and CRC) was determined by logistic regression methods adjusted for expected CRC incidence rate, prior history of AA, patient age and sex on a training subset. A linear predictor was developed to generate a score scaled from 0-100. The test performance was evaluated on an independent set of subjects using pre-specified algorithms and cutpoint. RESULTS Based on a pre-defined clinical threshold and predictive model derived from the training set (n=232), analysis of an independent asymptomatic validation set (n=194) yielded 89% (Lower exact one-sided 95% CI: 80%) specificity and 100% (95% CI: 37%)/78% (95% CI: 61%) sensitivity for detection of CRC/AA. In a secondary analysis, excluding surveillance subjects, the 97-subject screening cohort yielded 91% (95% CI: 79%) specificity and CRC/AA sensitivity at 100% (95% CI:37%)/83% (95% CI: 56%, 87% for advanced neoplasia 95% CI: 64%). Significant associations, (p CONCLUSIONS A multimodal blood test that included CEC and somatic mutations with adjustment for age and sex demonstrated high sensitivity for the diagnosis of advanced colorectal neoplasia. The resulting score captures prognostic information for CRC progression of index adenoma size and number and has the potential to enable stratification of patients for screening or post- polypectomy surveillance colonoscopy.

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Background Viable knowledge translation (KT) strategies are increasingly sought to improve asthma diagnosis, particularly in primary care. Despite this understanding, practical KT tools to support primary care practitioners are not widely available. Electronic medical records (EMRs) offer an opportunity to optimize the diagnosis and surveillance of chronic diseases such as asthma, and support quality improvement initiatives that increase adherence to guideline-recommended care. This review aims to describe the current state of electronic KT electronic tools (eTools) and surveillance systems for asthma and identify opportunities to increase adherence to asthma diagnostic guidelines by implementing digital KT eTools. Methods Systematic literature searches were conducted on Ovid MEDLINE that included the search terms: asthma, asthma diagnosis, asthma surveillance, electronic health records, translational medical research, quality improvement, professional practice gaps, and primary health care published in the previous 10 years. In total, the searches returned 971 articles, 163 of which were considered relevant and read in full. An additional 28 articles were considered after reviewing the references from selected articles. 75 articles were included in this narrative review. Results Established KT eTools for asthma such as electronic questionnaires, computerized clinical decision support systems (CDSS), chronic disease surveillance networks, and asthma registries have been effective in improving the quality of asthma diagnosis and care. As well, chronic disease surveillance systems, severe asthma registries, and workplace asthma surveillance systems have demonstrated success in monitoring asthma outcomes. However, lack of use and/or documentation of objective measures of lung function, challenges in identifying asthma cases in EMRs, and limitations of data sources have created barriers in the development of KT eTools. Existing digital KT eTools that overcome these data quality limitations could provide an opportunity to improve adherence to best-practice guidelines for asthma diagnosis and management. Conclusion Future initiatives in the development of KT eTools for asthma care should focus on strategies that assist healthcare providers in accurately diagnosing and documenting cases of asthma. A digital asthma surveillance system could support adherence to best-practice guidelines of asthma diagnosis and surveillance by prompting use of objective methods of confirmation to confirm an asthma diagnosis within the EMR.

Respiratory self-care places considerable demands on patients with chronic airways disease (AD), as they must obtain, understand and apply information required to follow their complex treatment plans. If clinical and lifestyle information overwhelms patients’ HL capacities, it reduces their ability to self-manage. This review outlines important societal, individual, and healthcare system factors that influence disease management and outcomes among patients with asthma and chronic obstructive pulmonary disease (COPD)—the two most common ADs. For this review, we undertook a comprehensive literature search, conducted reference list searches from prior HL-related publications, and added insights from international researchers and scientists with an interest in HL. We identified methodological limitations in currently available HL measurement tools in respiratory care. We also summarized the issues contributing to low HL and system-level cultural incompetency that continue to be under-recognized in AD management and contribute to suboptimal patient outcomes. Given that impaired HL is not commonly recognized as an important factor in AD care, we propose a three-level patient-centered model (strategies) designed to integrate HL considerations, with the goal of enabling health systems to enhance service delivery to meet the needs of all AD patients.

Strong evidence demonstrates the protective benefit of frequent colonoscopy surveillance for colorectal cancer prevention in Lynch Syndrome (LS) and is endorsed by many guidelines. Until recently, the evidence supporting the utility of upper endoscopy [esophagogastroduodenoscopy (EGD)] for upper gastrointestinal (UGI) cancer surveillance was limited. Over the last 3 years, multiple studies have demonstrated that EGD surveillance in LS is associated with the detection of both precancerous lesions and early-stage UGI cancers. On the basis of the emerging favorable evidence derived from EGD surveillance programs, the 2022 National Comprehensive Cancer Network (NCCN) Guidelines for LS recommend UGI surveillance with EGD starting between age 30 and 40 years with repeat EGDs every 2 to 4 years, preferably in conjunction with colonoscopy, in all patients with a germline pathogenic variant (PV) in MLH1, MSH2, EPCAM, and MSH6 and, because of the lack of data, consideration in PMS2. Standardization of the approach to performing EGD surveillance in LS and reporting clinically actionable findings is requisite for both improving quality and understanding the cost efficiency and outcomes of patients undergoing EGD as a surveillance tool. Accordingly, the primary objective of this Quality of Upper Endoscopy in Lynch Syndrome (QUELS) statement is to articulate a framework for standardizing the approach to performing and reporting EGD findings in patients with LS by introducing emerging quality metrics. The recommendations presented herein were developed from available evidence and consensus-based expert opinion and provide a practical approach for clinicians applying EGD surveillance in accordance with the most recent and existing LS guidelines.