Value of genetic testing for pediatric epilepsy: Driving earlier diagnosis of ceroid lipofuscinosis type 2 Batten disease.

This study assessed the effectiveness of genetic testing in shortening the time to diagnosis of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease. Individuals who received epilepsy gene panel testing through Behind the Seizure® , a sponsored genetic testing program (Cohort A), were compared to children outside of the sponsored testing program during the same period (Cohort B). Two cohorts were analyzed: children aged ≥24 to ≤60 months with unprovoked seizure onset at ≥24 months between December 2016 and January 2020 (Cohort 1) and children aged 0 to ≤60 months at time of testing with unprovoked seizure onset at any age between February 2019 and January 2020 (Cohort 2). The diagnostic yield in Cohort 1A (n = 1814) was 8.4% (n = 153). The TPP1 diagnostic yield within Cohort 1A was 2.9-fold higher compared to Cohort 1B (1.0%, n = 18/1814 vs. .35%, n = 8/2303; p = .0157). The average time from first symptom to CLN2 disease diagnosis was significantly shorter than previously reported (9.8 vs. 22.7 months, p < .001). These findings indicate that facilitated access to early epilepsy gene panel testing helps to increase diagnostic yield for CLN2 disease and shortens the time to diagnosis, enabling earlier intervention.

Rate of detection of serrated lesions at colonoscopy in an average-risk population: a meta-analysis of 129,001 individuals.

Background and study aims Serrated lesions are precursors of approximately one-third of colorectal cancers (CRCs). Information on their detection rate was lacking as an important reference for CRC screening. This study was a systematic review and meta-analysis to determine the overall detection rate for serrated lesions and their subtypes in average-risk populations undergoing CRC screening with colonoscopy. Patient and methods MEDLINE and Embase were searched to identify population-based studies that reported the detection rate for serrated lesions. Studies on average-risk populations using colonoscopy as a screening tool were included. Metaprop was applied to model within-study variability by binomial distribution, and Freeman-Tukey Double Arcsine Transformation was adopted to stabilise the variances. The detection rate was presented in proportions using random-effects models. Results In total, 17 studies involving 129,001 average-risk individuals were included. The overall detection rates for serrated lesions (19.0 %, 95 % CI = 15.3 %-23.0 %), sessile serrated polyps (2.5 %, 95 % CI = 1.5 %-3.8 %), and traditional serrated adenomas (0.3 %, 95 % CI = 0.1 %-0.8 %) were estimated. Subgroup analysis indicated a higher detection rate for serrated lesions among males (22.0 %) than females (14.0 %), and Caucasians (25.9 %) than Asians (14.6 %). The detection rate for sessile serrated polyps was also higher among Caucasians (2.9 %) than Asians (0.7 %). Conclusions This study determined the overall detection rate for serrated lesions and their different subtypes. The pooled detection rate estimates can be used as a reference for establishing CRC screening programs. Future studies may evaluate the independent factors associated with the presence of serrated lesions during colonoscopy to enhance their rate of detection.

Factors associated with participation in colorectal cancer screening: A population-based study of 7200 individuals.

OBJECTIVE: This study aimed to evaluate how the knowledge and perception towards colorectal cancer (CRC) screening had been changed in a large population, and identified factors associated with its participation based on factors pertinent to the Health Belief Model (HBM). METHODS: Data from 3600 screening participants and 3600 non-participants were collected through a telephone survey via simple random sampling of telephone numbers in a territory-wide directory from December 2016 to November 2018. Sociodemographic factors; the enabling factors of screening as well as the barriers of screening were collected. The changes in these factors were evaluated by Pearson's chi-square trend test. A logistic regression model was constructed to identify the association between the above factors and CRC screening participation. RESULTS: The knowledge level (67.9% to 85.4%, p < 0.001), perceived severity of having CRC (37.7%-42.8%, p < 0.01), perceived benefits of screening (54.9%-72.1%, p < 0.001), and reductions in barriers (14.1%-5.1%, p < 0.001) of CRC screening significantly improved among the non-users. Subjects with older age (adjusted odds ratio (AOR): 2.01, p < 0.001), higher knowledge level of screening methods (AOR: 6.68, p < 0.001), greater perceived severity (AOR: 2.04, p < 0.001) and coverage of insurance (AOR: 1.22, p < 0.01) were more likely to participate. In contrast, more affluent subjects (AOR: 0.69, p < 0.001), female individuals (AOR: 0.63, p < 0.001), higher level of perceived psychological (AOR: 0.54, p < 0.001) and access barriers (AOR: 0.55, p < 0.001) were associated with poorer participation. CONCLUSION: These findings demonstrated a substantial increase in the enabling factors of CRC screening, including knowledge, perceived severity and perceived benefits. The study also identified the target groups such as younger individuals, females and more affluent people among whom more intensive educational initiatives are needed to enhance their participation.

Does theory of planned behaviour play a role in predicting uptake of colorectal cancer screening? A cross-sectional study in Hong Kong.

OBJECTIVE: Colorectal cancer (CRC) ranked second in terms of cancer mortality worldwide. It is associated with a substantial global disease burden. We aimed to examine whether the theory of planned behaviour (TPB) could predict the uptake of faecal immunochemical test to inform novel strategies for enhancing CRC screening participation in population-based programmes. DESIGN: Cross-sectional study. SETTINGS: A Hong Kong-based and territory-wide telephone survey was conducted during the study period from October 2017 to November 2018. PARTICIPANTS: 4800 asymptomatic individuals aged 61-70 years who can communicate in Cantonese were recruited during the survey period. Those who had a history of CRC, chronic bowel inflammation, two or more first-degree relatives with CRC, and received colonoscopy in the past 10 years or faecal occult blood test in the past 5 years were excluded. OUTCOME MEASURES: The association between CRC screening uptake and the factors pertinent to TPB was analysed by univariable and multivariable regression models and the mediating effect of intention. We adjusted for age, gender, educational level, marital and working status, as well as household income. RESULTS: Multivariable regression analysis showed that high perceived behavioural control (adjusted OR (AOR)=12.35, 95% CI 8.21 to 18.60, p<0.001), high intention for CRC screening (AOR=7.86, 95% CI 6.60 to 9.36, p<0.001) and positive attitude towards CRC screening (accuracy and effectiveness: AOR=1.19, 95% CI 1.03 to 1.38, p<0.05; embarrassment and apprehension: AOR=4.27, 95% CI 3.13 to 5.82, p<0.001) were significantly associated with CRC screening uptake. Mediation analysis found that the effect of social norms on screening behaviour was primarily mediated by intention (83.2%), and this indirect, mediated effect accounted for 21.7% to 24.1% of total effects of other constructs in TPB on screening behaviour. CONCLUSIONS: The variables pertinent to TPB could successfully predict CRC screening uptake. Promotion of CRC screening based on interventions that increase perceived behavioural control and behavioural intention could potentially enhance screening uptake. Further studies are needed to establish the cause and effect relationship among these variables and screening uptake, as well as to evaluate the cost-effectiveness of such interventions.

Global Prevalence of Colorectal Neoplasia: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Most colorectal cancers (CRC) arise from colorectal adenomas, yet there is not enough information on global prevalence to inform health care policy. We examined the prevalence of any type of adenomas, advanced adenomas (AADs), and CRC according to age, sex, ethnicity, geographic regions, and anatomic location (proximal vs distal). METHODS: MEDLINE and Embase were searched from their inception through May 1, 2018, to identify population-based, observational studies that reported the prevalence of colorectal neoplasia. Studies on participants 15 years or older, with a sample size of 500 persons or more, were included. Metaprop (College Station, TX) was used to model within-study variability by binomial distribution and Freeman-Tukey Double Arcsine Transformation to stabilize the variances. The prevalence figures were presented by proportions and their 95% CIs using random-effects models. RESULTS: Our meta-analysis included 70 studies involving 637,414 individuals. The overall prevalence rates of adenoma (23.9%; 95% CI, 22.2%-25.8%), AAD (4.6%; 95% CI, 3.8%-5.5%), and CRC (0.4%, 95% CI, 0.3%-0.5%) were calculated. Subgroup analysis indicated that prevalence values (adenomas, AADs, and CRCs) were higher among men (29.7%, 6.5%, and 0.8%, respectively) than women (19.3%, 3.8% and 0.4%, respectively), among older adults (25.9%, 5.2%, and 0.6%, respectively) than younger adults (14.6%, 1.6%, and 0.1%, respectively), among Caucasians (23.7%, 6.6%, and 0.5%, respectively) than other ethnicities, in European countries (25.9%, 8.4%, and 0.8%, respectively) than other countries, and among patients with proximal (25.9%, 5.3%, and 0.1%, respectively) vs distal neoplasia. CONCLUSIONS: In a systematic review and meta-analysis, we found a high prevalence of colorectal neoplasia among some populations. This indicates a need to expand CRC screening programs for these groups. The pooled prevalence estimates can be used as quality indicators for established CRC screening programs.

High frequency of germline TP53 mutations in a prospective adult-onset sarcoma cohort.

Sarcomas are a key feature of Li-Fraumeni and related syndromes (LFS/LFL), associated with germline TP53 mutations. Current penetrance estimates for TP53 mutations are subject to significant ascertainment bias. The International Sarcoma Kindred Study is a clinic-based, prospective cohort of adult-onset sarcoma cases, without regard to family history. The entire cohort was screened for mutations in TP53 using high-resolution melting analysis and Sanger sequencing, and multiplex-ligation-dependent probe amplification and targeted massively parallel sequencing for copy number changes. Pathogenic TP53 mutations were detected in blood DNA of 20/559 sarcoma probands (3.6%); 17 were germline and 3 appeared to be somatically acquired. Of the germline carriers, one appeared to be mosaic, detectable in the tumor and blood, but not epithelial tissues. Germline mutation carriers were more likely to have multiple cancers (47% vs 15% for non-carriers, P = 3.0×10(-3)), and earlier cancer onset (33 vs 48 years, P = 1.19×10(-3)). The median survival of mutation carriers following first cancer diagnosis was not significantly different from non-carriers. Only 10/17 (59%) pedigrees met classical or Chompret criteria for LFS. In summary, germline TP53 mutations are not rare in adult patients with sarcoma, with implications for screening, surveillance, treatment and genetic counselling of carriers and family members.