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1.
Gastroenterology ; 166(5): 743-757, 2024 05.
Article in English | MEDLINE | ID: mdl-38224860

ABSTRACT

One goal of colorectal cancer (CRC) screening is to prevent CRC incidence by removing precancerous colonic polyps, which are detected in up to 50% of screening examinations. Yet, the lifetime risk of CRC is 3.9%-4.3%, so it is clear that most of these individuals with polyps would not develop CRC in their lifetime. It is, therefore, a challenge to determine which individuals with polyps will benefit from follow-up, and at what intervals. There is some evidence that individuals with advanced polyps, based on size and histology, benefit from intensive surveillance. However, a large proportion of individuals will have small polyps without advanced histologic features (ie, "nonadvanced"), where the benefits of surveillance are uncertain and controversial. Demand for surveillance will further increase as more polyps are detected due to increased screening uptake, recent United States recommendations to expand screening to younger individuals, and emergence of polyp detection technology. We review the current understanding and clinical implications of the natural history, biology, and outcomes associated with various categories of colon polyps based on size, histology, and number. Our aims are to highlight key knowledge gaps, specifically focusing on certain categories of polyps that may not be associated with future CRC risk, and to provide insights to inform research priorities and potential management strategies. Optimization of CRC prevention programs based on updated knowledge about the future risks associated with various colon polyps is essential to ensure cost-effective screening and surveillance, wise use of resources, and inform efforts to personalize recommendations.


Subject(s)
Colonic Polyps , Colonoscopy , Colorectal Neoplasms , Early Detection of Cancer , Humans , Colonic Polyps/pathology , Colonic Polyps/diagnosis , Colonic Polyps/epidemiology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/prevention & control , Early Detection of Cancer/methods , Risk Factors , Risk Assessment
2.
Gastroenterology ; 167(2): 378-391, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38552670

ABSTRACT

BACKGROUND & AIMS: Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation. METHODS: Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMSmin) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses. RESULTS: CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation. CONCLUSIONS: CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.


Subject(s)
Colonoscopy , Colorectal Neoplasms , Cost-Benefit Analysis , Early Detection of Cancer , Occult Blood , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/economics , Colonoscopy/economics , Early Detection of Cancer/economics , Early Detection of Cancer/methods , Liquid Biopsy/economics , Biomarkers, Tumor/blood , Biomarkers, Tumor/analysis , Markov Chains , Quality-Adjusted Life Years , Middle Aged , Male , Female , Aged , Feces/chemistry , United States , Incidence , Predictive Value of Tests , Comparative Effectiveness Research , Health Care Costs
3.
Gastroenterology ; 167(2): 368-377, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38552671

ABSTRACT

BACKGROUND & AIMS: A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. METHODS: Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. RESULTS: Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. CONCLUSION: Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening.


Subject(s)
Colonoscopy , Colorectal Neoplasms , Cost-Benefit Analysis , Early Detection of Cancer , Occult Blood , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/economics , Middle Aged , Aged , United States , Early Detection of Cancer/economics , Early Detection of Cancer/methods , Female , Male , Colonoscopy/economics , Colonoscopy/statistics & numerical data , Centers for Medicare and Medicaid Services, U.S. , Quality-Adjusted Life Years , Sensitivity and Specificity , Predictive Value of Tests , Feces/chemistry , Computer Simulation , Models, Economic
4.
Ann Neurol ; 96(1): 175-186, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38721759

ABSTRACT

OBJECTIVE: This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). METHODS: EEG amplitude and power features were derived from the resting EEG of 60 females with RTT (median age = 10.7 years) and 26 neurotypical females (median age = 10.6 years). Analyses focus on group differences and within the RTT group, associations between the EEG parameters and clinical severity. For a subset of participants (n = 20), follow-up data were available for assessing the reproducibility of the results and the stability in the parameters over 1 year. RESULTS: Compared to neurotypical participants, participants with RTT had greater amplitude variability and greater low-frequency activity as reflected by greater delta power, more negative 1/f slope, and lower theta/delta, alpha/delta, beta/delta, alpha/theta, and beta/theta ratios. Greater delta power, more negative 1/f slope, and lower power ratios were associated with greater severity. Analyses of year 1 data replicated the associations between 1/f slope and power ratios and clinical severity and demonstrated good within-subject consistency in these measures. INTERPRETATION: Overall, group comparisons reflected a greater predominance of lower versus higher frequency activity in participants with RTT, which is consistent with prior clinical interpretations of resting EEG in this population. The observed associations between the EEG power measures and clinical assessments and the repeatability of these measures underscore the potential for EEG to provide an objective measure of cortical function and clinical severity for RTT. ANN NEUROL 2024;96:175-186.


Subject(s)
Electroencephalography , Rett Syndrome , Severity of Illness Index , Humans , Female , Electroencephalography/methods , Child , Adolescent , Rett Syndrome/physiopathology , Rett Syndrome/diagnosis , Young Adult , Adult , Brain Waves/physiology , Reproducibility of Results
5.
Gastroenterology ; 162(3): 952-956, 2022 03.
Article in English | MEDLINE | ID: mdl-35094786

ABSTRACT

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update Commentary is to review the available evidence and provide expert advice regarding the approach to using noninvasive colorectal cancer (CRC) screening options, including evidence for their effectiveness, selection of individuals for whom these tests are appropriate, implications of a positive non-colonoscopy screening test, and opportunities to enhance the quality of noninvasive CRC screening programs. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This expert commentary reflects recently published studies in this field, as well as the experiences of the authors who are gastroenterologists with high-level expertise in CRC screening and prevention.


Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , DNA/analysis , Early Detection of Cancer/methods , Occult Blood , Adenoma/blood , Adenoma/urine , Colorectal Neoplasms/blood , Colorectal Neoplasms/urine , DNA/blood , DNA Methylation , Feces/chemistry , Humans , Patient Selection , Practice Guidelines as Topic , Risk Assessment , Septins/genetics
6.
JAMA ; 330(18): 1760-1768, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37870871

ABSTRACT

Importance: Noninvasive tests for colorectal cancer screening must include sensitive detection of colorectal cancer and precancerous lesions. These tests must be validated for the intended-use population, which includes average-risk individuals 45 years or older. Objective: To evaluate the sensitivity and specificity of a noninvasive, multitarget stool RNA (mt-sRNA) test (ColoSense) test compared with results from a colonoscopy. Design, Setting, and Participants: This phase 3 clinical trial (CRC-PREVENT) was a blinded, prospective, cross-sectional study to support a premarket approval application for a class III medical device. A total of 8920 participants were identified online using social media platforms and enrolled from June 2021 to June 2022 using a decentralized nurse call center. All participants completed the mt-sRNA test, which incorporated a commercially available fecal immunochemical test (FIT), concentration of 8 RNA transcripts, and participant-reported smoking status. Stool samples were collected prior to participants completing a colonoscopy at their local endoscopy center. The mt-sRNA test results (positive or negative) were compared with index lesions observed on colonoscopy. Over the course of 12 months, individuals 45 years and older were enrolled in the clinical trial using the decentralized recruitment strategy. Participants were enrolled from 49 US states and obtained colonoscopies at more than 3800 different endoscopy centers. Main Outcomes and Measures: The primary outcomes included the sensitivity of the mt-sRNA test for detecting colorectal cancer and advanced adenomas and the specificity for no lesions on colonoscopy. Results: The mean (range) age of participants was 55 (45-90) years, with 4% self-identified as Asian, 11% as Black, and 7% as Hispanic. Of the 8920 eligible participants, 36 (0.40%) had colorectal cancer and 606 (6.8%) had advanced adenomas. The mt-sRNA test sensitivity for detecting colorectal cancer was 94%, sensitivity for detecting advanced adenomas was 46%, and specificity for no lesions on colonoscopy was 88%. The mt-sRNA test showed significant improvement in sensitivity for colorectal cancer (94% vs 78%; McNemar P = .01) and advanced adenomas (46% vs 29%; McNemar P < .001) compared with results of the FIT. Conclusions and Relevance: In individuals 45 years and older, the mt-sRNA test showed high sensitivity for colorectal neoplasia (colorectal cancer and advanced adenoma) with significant improvement in sensitivity relative to the FIT. Specificity for no lesions on colonoscopy was comparable to existing molecular diagnostic tests. Trial Registration: ClinicalTrials.gov Identifier: NCT04739722.


Subject(s)
Adenoma , Colonoscopy , Colorectal Neoplasms , Feces , RNA , Aged , Aged, 80 and over , Humans , Middle Aged , Adenoma/diagnosis , Adenoma/genetics , Adenoma/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Cross-Sectional Studies , Early Detection of Cancer/methods , Feces/chemistry , Mass Screening/methods , Occult Blood , Prospective Studies , RNA, Small Untranslated/analysis , RNA/analysis , Immunochemistry
7.
Entropy (Basel) ; 25(8)2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37628218

ABSTRACT

Currently, renewable energies, including wind energy, have been experiencing significant growth. Wind energy is transformed into electric energy through the use of wind turbines (WTs), which are located outdoors, making them susceptible to harsh weather conditions. These conditions can cause different types of damage to WTs, degrading their lifetime and efficiency, and, consequently, raising their operating costs. Therefore, condition monitoring and the detection of early damages are crucial. One of the failures that can occur in WTs is the occurrence of cracks in their blades. These cracks can lead to the further deterioration of the blade if they are not detected in time, resulting in increased repair costs. To effectively schedule maintenance, it is necessary not only to detect the presence of a crack, but also to assess its level of severity. This work studies the vibration signals caused by cracks in a WT blade, for which four conditions (healthy, light, intermediate, and severe cracks) are analyzed under three wind velocities. In general, as the proposed method is based on machine learning, the vibration signal analysis consists of three stages. Firstly, for feature extraction, statistical and harmonic indices are obtained; then, the one-way analysis of variance (ANOVA) is used for the feature selection stage; and, finally, the k-nearest neighbors algorithm is used for automatic classification. Neural networks, decision trees, and support vector machines are also used for comparison purposes. Promising results are obtained with an accuracy higher than 99.5%.

8.
Gut ; 71(11): 2152-2166, 2022 11.
Article in English | MEDLINE | ID: mdl-36002247

ABSTRACT

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.


Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Adenoma/diagnosis , Adenoma/epidemiology , Adenoma/surgery , Asia/epidemiology , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Consensus , Early Detection of Cancer , Humans
9.
N Engl J Med ; 381(16): 1513-1523, 2019 10 17.
Article in English | MEDLINE | ID: mdl-31618539

ABSTRACT

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).


Subject(s)
Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/surgery , Heartburn/drug therapy , Omeprazole/therapeutic use , Proton Pump Inhibitors/therapeutic use , Adult , Baclofen/therapeutic use , Desipramine/therapeutic use , Drug Resistance , Drug Therapy, Combination , Female , Fundoplication , Gastroesophageal Reflux/complications , Heartburn/etiology , Heartburn/surgery , Humans , Male , Middle Aged , Muscle Relaxants, Central/therapeutic use , Quality of Life , Surveys and Questionnaires , Veterans
10.
Gastroenterology ; 161(4): 1145-1155.e12, 2021 10.
Article in English | MEDLINE | ID: mdl-34119517

ABSTRACT

BACKGROUND & AIMS: Incidence and mortality associated with early-age onset colorectal cancer (EAO-CRC) is increasing, prompting professional society recommendations to lower the screening age in average-risk individuals. The yield of screening individuals younger than 50 years is not known. METHODS: A systematic review of 3 databases from inception through July 2020 was performed in all languages that reported colonoscopy findings in average-risk individuals younger than 50 years. The primary outcomes were EAO colorectal neoplasia (CRN) and advanced colorectal neoplasia (aCRN) prevalence. Subgroup analyses were performed based on sex, geographic location, time period, and age, including comparison with those aged 50-59 years. Generalized linear mixed model with random intercept logistic regression and fixed subgroup effects were performed. RESULTS: Of 10,123 unique articles, 17 studies published between 2002 and 2020, including 51,811 average-risk individuals from 4 continents, were included. The pooled rate of EAO-CRN was 13.7% (95% confidence interval [CI], 0.112%-0.168%) and EAO-aCRN was 2.2% (95% CI, 0.016%-0.031%). Prevalence of CRC was 0.05% (95% CI, 0.00029%-0.0008%). Rates of EAO-CRN were higher in men compared with women (relative risk, 1.71%; 95% CI, 1.49%-1.98%), and highest in the United States (15.6%; 95% CI, 12.2%-19.7%) compared with Europe (14.9%; 95% CI, 6.9%-29.3%), East Asia (13.4%; 95% CI, 10.3%-17.2%), and the Middle East (9.8%; 95% CI, 7.8%-12.2%) (P = .04) The rate of EAO-CRN in age groups 45-49 years and 50-59 years was 17.8% (95% CI, 14.5%-21.6%) and 24.8% (95% CI, 19.5%-30.8%), respectively (P = .04). The rate of EAO-aCRN in age group 45-49 years was 3.6% (95% CI, 1.9%-6.7%) and 4.2% (95% CI, 3.2%-5.7%), respectively (P = .69). CONCLUSIONS: The rate of aCRN in individuals aged 45-49 years was similar to the rate observed in individual aged 50-59 years, suggesting that expanding screening to this population could yield a similar impact on colorectal cancer risk reduction.


Subject(s)
Colonoscopy , Colorectal Neoplasms/pathology , Early Detection of Cancer , Adult , Age of Onset , Colorectal Neoplasms/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Predictive Value of Tests , Prevalence , Risk Assessment , Risk Factors
11.
Clin Gastroenterol Hepatol ; 20(10): 2198-2209.e3, 2022 10.
Article in English | MEDLINE | ID: mdl-35688352

ABSTRACT

In 2018, the American Gastroenterological Association's Center for GI Innovation and Technology convened a consensus conference, entitled "Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes." The conference participants, which included more than 60 experts in colorectal cancer, considered recent improvements in colorectal cancer screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes.


Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Adenoma/diagnosis , Colonic Polyps/diagnosis , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Early Detection of Cancer , Humans , Mass Screening
12.
J Pediatr ; 244: 169-177.e3, 2022 05.
Article in English | MEDLINE | ID: mdl-35063470

ABSTRACT

OBJECTIVE: To characterize growth and anthropometric measurements in females with Rett syndrome and compare these measurements with functional outcomes. STUDY DESIGN: We obtained longitudinal growth and anthropometric measurements from 1154 females with classic and atypical Rett syndrome seen between 2006 and 2019 in the US Natural History Study. We calculated the Clinical Severity Score, Motor Behavior Assessment score, and arm and leg muscle areas and recorded the functional assessments of arm and hand use and ambulation. We compared growth and anthropometric variables from females with Rett syndrome in regard to normative data. We analyzed Clinical Severity Score, Motor Behavior Assessment, and anthropometric measurements in regard to functional assessments. RESULTS: Growth and anthropometric measurements were significantly lower in females with classic and severe atypical Rett syndrome compared with those classified as mild atypical Rett syndrome and deviated from normative patterns among all 3 groups. Suprailiac skinfold measurements correlated with body mass index measurements in each group. Lower leg muscle area measurements were significantly greater among females in all 3 Rett syndrome groups who ambulated independently compared with those who did not. In females with classic Rett syndrome, arm, thigh, and lower leg muscle area measurements increased significantly over time and were significantly greater among those who had purposeful arm and hand use and independent ambulation compared with those who did not. CONCLUSIONS: The pattern of growth and anthropometric measures in females with Rett syndrome differs from normative data and demonstrates clear differences between classic and mild or severe atypical Rett syndrome. Anthropometric measures correspond with functional outcomes and could provide markers supporting efficacy outcomes in clinical trials.


Subject(s)
Rett Syndrome , Anthropometry , Female , Humans , Male , Methyl-CpG-Binding Protein 2 , Walking/physiology
13.
Ann Neurol ; 89(4): 790-802, 2021 04.
Article in English | MEDLINE | ID: mdl-33480039

ABSTRACT

OBJECTIVE: The aim of the current study was to evaluate the utility of evoked potentials as a biomarker of cortical function in Rett syndrome (RTT). As a number of disease-modifying therapeutics are currently under development, there is a pressing need for biomarkers to objectively and precisely assess the effectiveness of these treatments. METHOD: Yearly visual evoked potentials (VEPs) and auditory evoked potentials (AEPs) were acquired from individuals with RTT, aged 2 to 37 years, and control participants across 5 sites as part of the Rett Syndrome and Related Disorders Natural History Study. Baseline and year 1 data, when available, were analyzed and the repeatability of the results was tested. Two syndrome-specific measures from the Natural History Study were used for evaluating the clinical relevance of the VEP and AEP parameters. RESULTS: At the baseline study, group level comparisons revealed reduced VEP and AEP amplitude in RTT compared to control participants. Further analyses within the RTT group indicated that this reduction was associated with RTT-related symptoms, with greater severity associated with lower VEP and AEP amplitude. In participants with RTT, VEP and AEP amplitude was also negatively associated with age. Year 1 follow-up data analyses yielded similar findings and evidence of repeatability of EPs at the individual level. INTERPRETATION: The present findings indicate the promise of evoked potentials (EPs) as an objective measure of disease severity in individuals with RTT. Our multisite approach demonstrates potential research and clinical applications to provide unbiased assessment of disease staging, prognosis, and response to therapy. ANN NEUROL 2021;89:790-802.


Subject(s)
Evoked Potentials , Rett Syndrome/physiopathology , Adolescent , Adult , Aging , Biomarkers , Cerebral Cortex/physiopathology , Child , Child, Preschool , Electroencephalography , Evoked Potentials, Auditory , Evoked Potentials, Visual , Female , Follow-Up Studies , Humans , Male , Severity of Illness Index , Young Adult
14.
Gastrointest Endosc ; 96(3): 553-562.e3, 2022 09.
Article in English | MEDLINE | ID: mdl-35533738

ABSTRACT

BACKGROUND AND AIMS: Data are limited regarding colonoscopy risk during long-term, programmatic colorectal cancer screening and follow-up. We aimed to describe adverse events during follow-up in a colonoscopy screening program after the baseline examination and examine factors associated with increased risk. METHODS: Cooperative Studies Program no. 380 includes 3121 asymptomatic veterans aged 50 to 75 years who underwent screening colonoscopy between 1994 and 1997. Periprocedure adverse events requiring significant intervention were defined as major events (other events were minor) and were tracked during follow-up for at least 10 years. Multivariable odds ratios (ORs) were calculated for factors associated with risk of follow-up adverse events. RESULTS: Of 3727 follow-up examinations in 1983 participants, adverse events occurred in 105 examinations (2.8%) in 93 individuals, including 22 major and 87 minor events (examinations may have had >1 event). Incidence of major events (per 1000 examinations) remained relatively stable over time, with 6.1 events at examination 2, 4.8 at examination 3, and 7.2 at examination 4. Examinations with major events included 1 perforation, 3 GI bleeds requiring intervention, and 17 cardiopulmonary events. History of prior colonoscopic adverse events was associated with increased risk of events (major or minor) during follow-up (OR, 2.7; 95% confidence interval, 1.6-4.6). CONCLUSIONS: Long-term programmatic screening and surveillance was safe, as major events were rare during follow-up. However, serious cardiopulmonary events were the most common major events. These results highlight the need for detailed assessments of comorbid conditions during routine clinical practice, which could help inform individual decisions regarding the utility of ongoing colonoscopy follow-up.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Colonoscopy/adverse effects , Colonoscopy/methods , Colorectal Neoplasms/epidemiology , Early Detection of Cancer/methods , Humans , Mass Screening , Prospective Studies , Risk Factors
15.
Endoscopy ; 54(9): 881-889, 2022 09.
Article in English | MEDLINE | ID: mdl-34979570

ABSTRACT

BACKGROUND: A high rate of neoplasia, both high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) has been reported in Barrett's esophagus at index endoscopy, but precise rates of post-endoscopy Barrett's neoplasia (PEBN) are unknown. METHODS: A systematic review and meta-analysis was performed examining electronic databases (inception to October 2021) for studies reporting PEBN. Consistent with the definitions of post-colonoscopy colorectal cancer proposed by the World Endoscopy Organization, we defined neoplasia (HGD/EAC) detected at index endoscopy and/or within 6 months of a negative index endoscopy as "prevalent" neoplasia, that detected after 6 months of a negative index endoscopy and prior to next surveillance interval (i. e. 3 years) as PEBN or "interval" neoplasia, and that detected after 36 months from a negative index endoscopy as "incident" neoplasia. The pooled incidence rates and proportions relative to total neoplasia were analyzed. RESULTS: 11 studies (n = 59 795; 61 % men; mean [SD] age 62.3 [3.3] years) met the inclusion criteria. The pooled incidence rates were: prevalent neoplasia 4.5 % (95 %CI 2.2 %-8.9 %) at baseline and an additional 0.3 % (0.1 %-0.7 %) within the first 6 months, PEBN 0.52 % (0.46 %-0.58 %), and incident neoplasia 1.4 % (0.9 %-2.1 %). At 3 years from the index endoscopy, PEBN accounted for 3 % of total Barrett's neoplasia, while prevalent neoplasia accounted for 97 %. CONCLUSION: Neoplasia detected at or within 6 months of index endoscopy accounts for most cases of Barrett's neoplasia (> 90 %). PEBN accounts for ~3 % of cases and can be used for validation in future. This highlights the importance of a high quality index endoscopy in Barrett's esophagus and the need to establish quality benchmarks to measure endoscopists' performance.


Subject(s)
Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Adenocarcinoma/diagnosis , Adenocarcinoma/epidemiology , Adenocarcinoma/etiology , Barrett Esophagus/pathology , Endoscopy, Gastrointestinal , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/etiology , Female , Humans , Male , Middle Aged
16.
Dig Dis Sci ; 67(6): 2526-2534, 2022 06.
Article in English | MEDLINE | ID: mdl-34089135

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) screening guidelines recommend frequent colonoscopies and consideration of genetic testing in individuals with ≥10 cumulative adenomas. However, it is unclear how these guidelines apply to routine practice. AIMS: We estimated the proportion of participants found to have ≥10 cumulative adenomas in a screening population and described their outcomes of advanced neoplasia (AN), CRC, and extra-colonic malignancy. METHODS: We performed a secondary analysis of VA CSP#380, which includes 3121 veterans aged 50-75 who were followed up to 10 years after screening colonoscopy. We calculated the cumulative risk of ≥10 cumulative adenomas by Kaplan-Meier method. We compared baseline risk factors in those with and without ≥10 cumulative adenomas as well as the risk for AN (adenoma ≥1 cm, villous adenoma or high-grade dysplasia, or CRC) and extra-colonic malignancy by multivariate logistic regression. RESULTS: The cumulative risk of ≥10 cumulative adenomas over 10.5 years was 6.51% (95% CI 4.38%-9.62%). Age 60-69 or 70-75 at baseline colonoscopy was the only factors associated with the finding of ≥10 cumulative adenomas. Compared to those with 0-9 cumulative adenomas, participants with ≥10 cumulative adenomas were more likely to have had AN (OR 17.03; 95% CI 9.41-30.84), including CRC (OR 7.00; 95% CI 2.84-17.28), but not extra-colonic malignancies. CONCLUSIONS: Approximately 6.5% of participants in this screening population were found to have ≥10 cumulative adenomas over 10.5 years, which was uncommon before age 60. These participants were found to have AN and CRC significantly more often compared to those with lower cumulative adenomas.


Subject(s)
Adenoma , Colonic Neoplasms , Colonic Polyps , Colorectal Neoplasms , Adenoma/diagnosis , Adenoma/epidemiology , Adenoma/pathology , Colonic Neoplasms/pathology , Colonic Polyps/pathology , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Early Detection of Cancer/methods , Humans , Incidence , Risk Factors
17.
Gastroenterology ; 158(2): 436-440, 2020 01.
Article in English | MEDLINE | ID: mdl-31614123

ABSTRACT

Colon polyp surveillance now accounts for 25% of all colonoscopies performed. The evidence that colonoscopy surveillance reduces colorectal cancer (CRC) incidence or mortality is weak. The biology of the baseline lesions and quality of the baseline exam are two primary factors contributing to post-colonoscopy CRC. Prior recommendations for surveillance were based largely on the likelihood that patients with adenomas would develop advanced adenomas, a surrogate for CRC. There is now evidence that baseline colonoscopy findings are strongly associated with the risk of incidence or death from CRC. This evidence provides a basis for updated evidence-based recommendations for surveillance. In addition, there is also growing evidence that the quality of the baseline exam is an important predictor of the likelihood of developing post-colonoscopy CRC.


Subject(s)
Adenomatous Polyps/pathology , Colonic Polyps/pathology , Colonoscopy , Colorectal Neoplasms/pathology , Early Detection of Cancer/methods , Adenomatous Polyps/epidemiology , Adenomatous Polyps/surgery , Colonic Polyps/epidemiology , Colonic Polyps/surgery , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/prevention & control , Disease Progression , Humans , Incidence , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors , Time Factors
18.
Gastroenterology ; 158(4): 862-874.e8, 2020 03.
Article in English | MEDLINE | ID: mdl-31376388

ABSTRACT

BACKGROUND & AIMS: Few studies have evaluated long-term outcomes of ongoing colonoscopic screening and surveillance in a screening population. We aimed to determine the 10-year risk for advanced neoplasia (defined as adenomas ≥10mm, adenomas with villous histology or high-grade dysplasia, or colorectal cancer [CRC]) and assessed whether baseline colonoscopy findings were associated with long-term outcomes. METHODS: We collected data from the Department of Veterans Affairs Cooperative Studies Program Study on 3121 asymptomatic veterans (50-75 years old) who underwent a screening colonoscopy from 1994 through 1997 at 13 medical centers and were then followed for 10 years or until death. We included 1915 subjects with at least 1 surveillance colonoscopy and estimated cumulative incidence of advanced neoplasia by Kaplan-Meier curves. We then fit a longitudinal joint model to estimate risk of advanced neoplasia at each subsequent examination after baseline, adjusting for multiple colonoscopies within individuals. RESULTS: Through 10 years of follow-up, there were 146 individuals among all baseline colonoscopy groups found to have at least 1 incident advanced neoplasia. The cumulative 10-year incidence of advanced neoplasia was highest among those with baseline CRC (43.7%; 95% CI 13.0%-74.4%), followed by those with baseline advanced adenoma (AA) (21.9%; 95% CI 15.7-28.1). The cumulative 10-year incidence of advanced neoplasia was 6.3% (95% CI 4.1%-8.5%) and 4.1% (95% CI 2.7%-5.4%) for baseline 1 to 2 small adenomas (<1cm, and without villous histology or high-grade dysplasia) and no neoplasia, respectively (log-rank P = .10). After adjusting for prior surveillance, the risk of advanced neoplasia at each subsequent examination was not significantly increased in veterans with 1 or 2 small adenomas at baseline (odds ratio 0.96; 95% CI 0.67-1.41) compared with veterans with no baseline neoplasia. CONCLUSIONS: Baseline screening colonoscopy findings associate with advanced neoplasia within 10 years. Individuals with only 1 or 2 small adenomas at baseline have a low risk of advanced neoplasia over 10 years. Alternative surveillance strategies, could be considered for these individuals.


Subject(s)
Adenoma/pathology , Colonic Polyps/pathology , Colonoscopy/statistics & numerical data , Colorectal Neoplasms/epidemiology , Early Detection of Cancer/statistics & numerical data , Adenoma/diagnostic imaging , Adenoma/surgery , Aged , Colon/diagnostic imaging , Colon/pathology , Colon/surgery , Colonic Polyps/diagnostic imaging , Colonic Polyps/surgery , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Incidence , Intestinal Mucosa/diagnostic imaging , Intestinal Mucosa/pathology , Intestinal Mucosa/surgery , Longitudinal Studies , Male , Mass Screening , Middle Aged , Neoplasm Staging , Prospective Studies , Retrospective Studies , Risk Assessment , Risk Factors , United States/epidemiology , United States Department of Veterans Affairs/statistics & numerical data , Veterans/statistics & numerical data
19.
Clin Gastroenterol Hepatol ; 19(5): 1038-1050, 2021 05.
Article in English | MEDLINE | ID: mdl-33493699

ABSTRACT

BACKGROUND & AIMS: There is a lack of clinical studies to establish indications and methodology for tattooing, therefore technique and practice of tattooing is very variable. We aimed to establish a consensus on the indications and appropriate techniques for colonic tattoo through a modified Delphi process. METHODS: The baseline questionnaire was classified into 3 areas: where tattooing should not be used (1 domain, 6 questions), where tattooing should be used (4 domains, 20 questions), and how to perform tattooing (1 domain 20 questions). A total of 29 experts participated in the 3 rounds of the Delphi process. RESULTS: A total of 15 statements were approved. The statements that achieved the highest agreement were as follows: tattooing should always be used after endoscopic resection of a lesion with suspicion of submucosal invasion (agreement score, 4.59; degree of consensus, 97%). For a colorectal lesion that is left in situ but considered suitable for endoscopic resection, tattooing may be used if the lesion is considered difficult to detect at a subsequent endoscopy (agreement score, 4.62; degree of consensus, 100%). A tattoo should never be injected directly into or underneath a lesion that might be removed endoscopically at a later point in time (agreement score, 4.79; degree of consensus, 97%). Details of the tattoo injection should be stated clearly in the endoscopy report (agreement score, 4.76; degree of consensus, 100%). CONCLUSIONS: This expert consensus has developed different statements about where tattooing should not be used, when it should be used, and how that should be done.


Subject(s)
Tattooing , Colon , Endoscopy , Humans
20.
Am J Gastroenterol ; 116(9): 1876-1884, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34140455

ABSTRACT

INTRODUCTION: Gastroenterologists at all levels of practice benefit from formal mentoring. Much of the current literature on mentoring in gastroenterology is based on expert opinion rather than data. In this study, we aimed to identify gender-related barriers to successful mentoring relationships from the mentor and mentee perspectives. METHODS: A voluntary, web-based survey was distributed to physicians at 20 academic institutions across the United States. Overall, 796 gastroenterology fellows and faculty received the survey link, with 334 physicians responding to the survey (42% response rate), of whom 299 (90%; 129 women and 170 men) completed mentorship questions and were included in analysis. RESULTS: Responses of women and men were compared. Compared with men, more women preferred a mentor of the same gender (38.6% women vs 4.2% men, P < 0.0001) but less often had one (45.5% vs 70.2%, P < 0.0001). Women also reported having more difficulty finding a mentor (44.4% vs 16.0%, P < 0.0001) and more often cited inability to identify a mentor of the same gender as a contributing factor (12.8% vs 0.9%, P = 0.0004). More women mentors felt comfortable advising women mentees about work-life balance (88.3% vs 63.8%, P = 0.0005). Nonetheless, fewer women considered themselves effective mentors (33.3% vs 52.6%, P = 0.03). More women reported feeling pressured to mentor because of their gender (39.5% vs 0.9% of men, P < 0.0001). Despite no gender differences, one-third of respondents reported negative impact of the COVID-19 pandemic on their ability to mentor and be mentored. DISCUSSION: Inequities exist in the experiences of women mentees and mentors in gastroenterology, which may affect career advancement and job satisfaction.


Subject(s)
Clinical Clerkship , Gastroenterology/education , Gender Equity , Mentoring , Adult , Female , Humans , Internet , Male , Surveys and Questionnaires , United States , Universities
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