Unveiling promising drug targets for autism spectrum disorder: insights from genetics, transcriptomics, and proteomics.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which current treatments are limited and drug development costs are prohibitive. Identifying drug targets for ASD is crucial for the development of targeted therapies. Summary-level data of expression quantitative trait loci obtained from GTEx, protein quantitative trait loci data from the ROSMAP project, and two ASD genome-wide association studies datasets were utilized for discovery and replication. We conducted a combined analysis using Mendelian randomization (MR), transcriptome-wide association studies, Bayesian colocalization, and summary-data-based MR to identify potential therapeutic targets associated with ASD and examine whether there are shared causal variants among them. Furthermore, pathway and drug enrichment analyses were performed to further explore the underlying mechanisms and summarize the current status of pharmacological targets for developing drugs to treat ASD. The protein-protein interaction (PPI) network and mouse knockout models were performed to estimate the effect of therapeutic targets. A total of 17 genes revealed causal associations with ASD and were identified as potential targets for ASD patients. Cathepsin B (CTSB) [odd ratio (OR) = 2.66 95, confidence interval (CI): 1.28-5.52, P = 8.84 × 10-3], gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) (OR = 1.99, 95CI: 1.06-3.75, P = 3.24 × 10-2), and formin like 1 (FMNL1) (OR = 0.15, 95CI: 0.04-0.58, P = 5.59 × 10-3) were replicated in the proteome-wide MR analyses. In Drugbank, two potential therapeutic drugs, Acamprosate (GABBR1 inhibitor) and Bryostatin 1 (CASP8 inhibitor), were inferred as potential influencers of autism. Knockout mouse models suggested the involvement of the CASP8, GABBR1, and PLEKHM1 genes in neurological processes. Our findings suggest 17 candidate therapeutic targets for ASD and provide novel drug targets for therapy development and critical drug repurposing opportunities.

Risks of digestive diseases in long COVID: evidence from a population-based cohort study.

BACKGROUND: In the post-pandemic era, a wide range of COVID-19 sequelae is of growing health concern. However, the risks of digestive diseases in long COVID have not been comprehensively understood. To investigate the long-term risk of digestive diseases among COVID patients. METHODS: In this large-scale retrospective cohort study with up to 2.6 years follow-up (median follow-up: 0.7 years), the COVID-19 group (n = 112,311), the contemporary comparison group (n = 359,671) and the historical comparison group (n = 370,979) predated the COVID-19 outbreak were built using UK Biobank database. Each digestive outcome was defined as the diagnosis 30 days or more after the onset of COVID-19 infection or the index date. Hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. RESULTS: Compared with the contemporary comparison group, patients with previous COVID-19 infection had higher risks of digestive diseases, including gastrointestinal (GI) dysfunction (HR 1.38 (95% CI 1.26 to 1.51)); peptic ulcer disease (HR 1.23 (1.00 to 1.52)); gastroesophageal reflux disease (GERD) (HR 1.41 (1.30 to 1.53)); gallbladder disease (HR 1.21 (1.06 to 1.38)); severe liver disease (HR 1.35 (1.03 to 1.76)); non-alcoholic liver disease (HR 1.27 (1.09 to 1.47)); and pancreatic disease (HR 1.36 (1.11 to 1.66)). The risks of GERD were increased stepwise with the severity of the acute phase of COVID-19 infection. Even after 1-year follow-up, GERD (HR 1.64 (1.30 to 2.07)) and GI dysfunction (HR 1.35 (1.04 to 1.75)) continued to pose risks to COVID-19 patients. Compared to those with one SARS-CoV-2 infection, reinfected patients were at a higher risk of pancreatic diseases (HR 2.57 (1.23 to 5.38)). The results were consistent when the historical cohort was used as the comparison group. CONCLUSIONS: Our study provides insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing digestive diseases. The risks exhibited a stepwise escalation with the severity of COVID-19, were noted in cases of reinfection, and persisted even after 1-year follow-up. This highlights the need to understand the varying risks of digestive outcomes in COVID-19 patients over time, particularly those who experienced reinfection, and develop appropriate follow-up strategies.

Prospective randomized controlled trial of water exchange plus cap versus water exchange colonoscopy in unsedated veterans.

BACKGROUND AND AIMS: Water exchange (WE) and cap-assisted colonoscopy separately have been shown to reduce pain during insertion in unsedated patients. We hypothesized that compared with WE, WE cap-assisted colonoscopy (WECAC) could significantly lower real-time maximum insertion pain (RTMIP). METHODS: Veterans without escort were recruited, randomized, blinded, and examined at 3 U.S. Veterans Affairs sites. The primary outcome was RTMIP, defined as the highest segmental pain (0 = no pain, 10 = most severe pain) during insertion. RESULTS: Randomization (WECAC, 143; WE, 137) produced an even distribution of a racially diverse group of men and women of low socioeconomic status. The intention-to-treat analysis reported results of WECAC and WE for cecal intubation (93% and 94.2%, respectively), mean RTMIP (2.9 [standard deviation {SD}, 2.5] and 2.6 [SD, 2.4]), proportion of patients with no pain (28.7% and 27.7%), mean insertion time (18.6 minutes [SD, 15.6] and 18.8 minutes [SD, 15.9]), and overall adenoma detection rate (48.3% and 55.1%); all P values were >.05. When RTMIP was binarized as "no pain" (0) versus "some pain" (1-10) or "low pain" (0-7) versus "high pain" (8-10), different significant predictors of RTMIP were identified. CONCLUSIONS: Unsedated colonoscopy was appropriate for unescorted veterans. WE alone was sufficient. Adding a cap did not reduce RTMIP. Patient-specific factors and application of WE with insertion suction of infused water contributed to high and low RTMIP, respectively. For unescorted patients, selecting those with low anxiety, avoiding low body mass index, history of depression or self-reported poor health, and complying with the steps of WE can minimize RTMIP to ensure success of unsedated colonoscopy. (Clinical trial registration number: NCT03160859.).

Comparison of Right Colon Flat Polyp Detection Rate by Water Exchange Versus Water Immersion-pooled Results of Data File of 3 Published Reports.

GOALS: We tested the hypothesis that water exchange (WE) achieved a significantly higher right colon flat polyp detection rate (rFPDR) than water immersion (WI). BACKGROUND: Current endoscopy methods provide real-time morphology but not histopathology. Flat serrated polyps are difficult to find during colonoscopy. In 2022 2 studies reported that the serrated polyp detection rate (SPDR) significantly inversely predicted the development of interval cancers. In 2021 1 systemic review with meta-analysis showed that WE, but not WI increased SPDR. The relative contributions of WE and WI on rFPDR are unknown. STUDY: Individual patient data from 3 reports comparing air insufflation, WI, and WE were pooled. Multiple logistic regression analysis was used to assess the factors associated with a higher rFPDR. RESULTS: The pooled data showed that the rFPDR of air insufflation, WI, and WE were 15.4%, 14.1%, and 19.4% ( P =0.009), respectively. After adjusting for age and withdrawal time, multiple logistic regression analysis revealed that WE, when compared with WI, was significantly associated with a higher rFPDR (adjusted odds ratio[aOR]=1.53, P =0.002). Analysis of data on pathology and size were omitted to avoid duplicating our earlier publications. CONCLUSIONS: Significantly higher rFPDR was achieved by WE. Water exchange rather than WI merits consideration for use to maximize rFPDR. Removal of flat polyps, and by inference serrated polyps, ensures their optimal management to minimize the occurrence of interval cancers. The potential benefit of WE in maximizing SPDR and minimizing interval cancers deserves evaluation in long-term randomized controlled studies focused on flat polyps detection.

Determination of the ideal plate for medial femoral condyle fracture fixation: an anatomical fit and biomechanical study.

BACKGROUND: The aim of this study is to determine the best plate to use as a substitute to fix a medial femoral condyle fracture. MATERIALS AND METHODS: The first part is to measure the best fit between several anatomical plates including the Proximal Tibia Anterolateral Plate (PT AL LCP), the Proximal Tibia Medial Plate (PT M LCP), the Distal Tibia Medial Locking Plate (DT M LCP) and the Proximal Humerus (PHILOS) plate against 28 freshly embalmed cadaveric distal femurs. Measurements such as plate offset and number of screws in the condyle and shaft shall be obtained. The subsequent part is to determine the compressive force at which the plate fails. After creating an iatrogenic medial condyle fracture, the cadavers will be fixed with the two plates with the best anatomical fit and subjected to a compression force using a hydraulic press. RESULTS: The PT AL LCP offered the best anatomical fit whereas the PHILOS plate offered the maximal number of screws inserted. The force required to create 2 mm of fracture displacement between the two is not statistically significant (LCP 889 N, PHILOS 947 N, p = 0.39). The PT AL LCP can withstand a larger fracture displacement than the PHILOS (LCP 24.4 mm, PHILOS 17.4 mm, p = 0.004). DISCUSSION AND CONCLUSION: Both the PT AL LCP and the PHILOS remain good options in fixing a medial femoral condyle fracture. Between the two, we would recommend the PT AL LCP as the slightly superior option.

Associations of habitual glucosamine use with SARS-CoV-2 infection and hospital admission and death with COVID-19: Evidence from a large population based cohort study.

The coronavirus disease 2019 (COVID-19) pandemic has led to a fundamental number of morbidity and mortality worldwide. Glucosamine was indicated to help prevent and control RNA virus infection preclinically, while its potential therapeutic effects on COVID-19-related outcomes are largely unknown. To assess the association of habitual glucosamine use with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, and mortality with COVID-19 in a large population based cohort. Participants from UK Biobank were reinvited between June and September 2021 to have SARS-CoV-2 antibody testing. The associations between glucosamine use and the risk of SARS-CoV-2 infection were estimated by logistic regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for COVID-19-related outcomes were calculated using COX proportional hazards model. Furthermore, we carried out propensity-score matching (PSM) and stratified analyses. At baseline, 42 673 (20.7%) of the 205 704 participants reported as habitual glucosamine users. During median follow-up of 1.67 years, there were 15 299 cases of SARS-CoV-2 infection, 4214 cases of COVID-19 hospital admission, and 1141 cases of COVID-19 mortality. The fully adjusted odds ratio of SARS-CoV-2 infection with glucosamine use was 0.96 (95% CI: 0.92-1.01). The fully adjusted HR were 0.80 (95% CI: 0.74-0.87) for hospital admission, and 0.81 (95% CI: 0.69-0.95) for mortality. The logistic regression and Cox proportional hazard analyses after PSM yielded consistent results. Our study demonstrated that habitual glucosamine use is associated with reduced risks of hospital admission and death with COVID-19, but not the incidence of SARS-CoV-2 infection.

Lack of Causal Associations of Inflammatory Bowel Disease with Parkinson's Disease and Other Neurodegenerative Disorders.

BACKGROUND: Observational studies have indicated associations between inflammatory bowel disease (IBD) and neurodegenerative diseases, including Parkinson's disease (PD). OBJECTIVE: To evaluate the causal associations of IBD with PD and other selected neurodegenerative disorders using updated data. METHODS: Bidirectional two-sample Mendelian randomization studies using genome-wide association studies summary statistics of IBD and PD. RESULTS: We found a lack of evidence for the causal association of IBD on PD (odds ratio [OR], 1.014; 95% confidence interval [CI], 0.967-1.063; P = 0.573). Reverse analysis also indicated no evidence of a causal effect for PD on IBD (OR, 0.978; 95% CI, 0.910-1.052; P = 0.549). The causality between IBD and Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis was unfounded (all P > 0.05). CONCLUSIONS: The updated analyses provide no clear evidence for causal associations of IBD with PD or the other three neurodegenerative diseases. Potential confounders might contribute to the previously observed associations, and further investigations are warranted. © 2023 International Parkinson and Movement Disorder Society.

Outcome of Water Exchange and Air Insufflation Colonoscopy Performed by Supervised Trainee and Their Assessment of the Training Experience.

GOALS: The hypotheses that supervised trainees would provide a more favorable assessment of the learning experience and could achieve superior results with water exchange (WE) compared with air insufflation were tested. BACKGROUND: WE decreased pain, increased cecal intubation rate (CIR), and polyp detection rate (PDR). STUDY: In a prospective pilot observational study, the trainees were taught WE in unsedated and WE and air insufflation in alternating order in sedated veterans. Trainee scores and procedural outcomes were tracked. RESULTS: 83 air insufflation and 119 WE cases were included. Trainee evaluations of the respective methods were scored based on a 5-point scale [1 (strongly agree) to 5 (strongly disagree, with lower scores being more favorable]. Evaluation scores [mean (SD)] were as follows: my colonoscopy experience was better than expected: WE 2.02 (1.00) versus air insufflation 2.43 (1.19), P =0.0087; I was confident with my technical skills using this method: WE 2.76 (0.91) versus air insufflation 2.85 (0.87), P =0.4822. Insertion time was 40 (21) min for WE and 30 (20) min for air insufflation ( P =0.0008). CIR were 95% (WE, unsedated); 99% (WE, overall), and 89% (air insufflation, overall). WE showed significantly higher CIR (99% vs. 89%, P =0.0031) and PDR (54% vs. 32%, P =0.0447). CONCLUSIONS: The long air insufflation insertion time indicated the trainees were inexperienced. The significantly longer WE insertion time confirmed that learning WE required extra time. This pilot study revealed that supervised trainees reported more favorable learning experience with WE and equivalent confidence in technical skills scores. They completed both unsedated and sedated colonoscopy in over 89% of cases achieved significantly higher CIR and PDR with WE than air insufflation. It appeared that trainee education in WE might be an acceptable alternative to augment air insufflation to meet the challenges of training posed by traditional air insufflation colonoscopy.

Mucin 13 (MUC13) as a candidate biomarker for ovarian cancer detection: potential to complement CA125 in detecting non-serous subtypes.

OBJECTIVES: Ovarian cancer is the most lethal gynecological malignancy in developed countries. One of the key associations with the high mortality rate is diagnosis at late stages. This clinical limitation is primarily due to a lack of distinct symptoms and detection at the early stages. The ovarian cancer biomarker, CA125, is mainly effective for identifying serous ovarian carcinomas, leaving a gap in non-serous ovarian cancer detection. Mucin 13 (MUC13) is a transmembrane, glycosylated protein with aberrant expression in malignancies, including ovarian cancer. We explored the potential of MUC13 to complement CA125 as an ovarian cancer biomarker, by evaluating its ability to discriminate serous and non-serous subtypes of ovarian cancer at FIGO stages I-IV from benign conditions. METHODS: We used our newly developed, high sensitivity ELISA to measure MUC13 protein in a large, well-defined cohort of 389 serum samples from patients with ovarian cancer and benign conditions. RESULTS: MUC13 and CA125 serum levels were elevated in malignant compared to benign cases (p<0.0001). Receiver-operating characteristic (ROC) curve analysis showed similar area under the curve (AUC) of 0.74 (MUC13) and 0.76 (CA125). MUC13 concentrations were significantly higher in mucinous adenocarcinomas compared to benign controls (p=0.0005), with AUC of 0.80. MUC13 and CA125 showed significant elevation in early-stage cases (stage I-II) in relation to benign controls (p=0.0012 and p=0.014, respectively). CONCLUSIONS: We report the novel role of MUC13 as a serum ovarian cancer biomarker, where it could complement CA125 for detecting some subtypes of non-serous ovarian carcinoma and early-stage disease.

Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups.

OBJECTIVES: Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. METHODS: Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. RESULTS: The percentage of POCT glucose tests performed without valid PPID ranged from 0-87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0-50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. CONCLUSIONS: Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

Polyp detection and false-positive rates by computer-aided analysis of withdrawal-phase videos of colonoscopy of the right-sided colon segment in a randomized controlled trial comparing water exchange and air insufflation.

BACKGROUND AND AIMS: Water exchange (WE) improves lesion detection but misses polyps because of human limitations. Computer-aided detection (CADe) identifies additional polyps overlooked by the colonoscopist. Additional polyp detection rate (APDR) is the proportion of patients with at least 1 additional polyp detected by CADe. The number of false positives (because of feces and air bubble) per colonoscopy (FPPC) is a major CADe limitation, which might be reduced by salvage cleaning with WE. We compared the APDR and FPPC by CADe between videos of WE and air insufflation in the right-sided colon. METHODS: CADe used a convolutional neural network with transfer learning. We edited and coded withdrawal-phase videos in a randomized controlled trial that compared right-sided colon findings between air insufflation and WE. Two experienced blinded endoscopists analyzed the CADe-overlaid videos and identified additional polyps by consensus. An artifact triggered by CADe but not considered a polyp by the reviewers was defined as a false positive. The primary outcome was APDR. RESULTS: Two hundred forty-five coded videos of colonoscopies inserted with WE (n = 123) and air insufflation (n = 122) methods were analyzed. The APDR in the WE group was significantly higher (37 [30.1%] vs 15 [12.3%], P = .001). The mean [standard deviation] FPPC related to feces (1.78 [1.67] vs 2.09 [2.09], P = .007) and bubbles (.53 [.89] vs 1.25 [2.45], P = .001) in the WE group were significantly lower. CONCLUSIONS: CADe showed significantly higher APDR and lower number of FPPC related to feces and bubbles in the WE group. The results support the hypothesis that the strengths of CADe and WE complement the weaknesses of each other in optimizing polyp detection.

GIE Editorial Board Top 10: advances in GI endoscopy in 2021.

The 9-member Editorial Board of the American Society for Gastrointestinal Endoscopy performed a systematic literature search of original articles published during 2021 in Gastrointestinal Endoscopy and 10 other high-impact medical and gastroenterology journals on endoscopy-related topics. Votes from each editorial board member were tallied to identify a consensus list of the 10 most significant topic areas in GI endoscopy over the calendar year of study, with a focus on 3 criteria: significance, novelty, and global impact on clinical practice. The 10 areas identified collectively represent advances in the following endoscopic topics: colonoscopy optimization, bariatric endoscopy, endoscopic needle sampling and drainage, peroral endoscopic myotomy, endoscopic defect closure, meeting systemic challenges in endoscopic training and practice, endohepatology, FNA versus fine-needle biopsy sampling, endoscopic mucosal and submucosal procedures, and cold snare polypectomy. Each board member contributed a summary of important articles relevant to 1 to 2 of the consensus topic areas, leading to a collective summary that is presented in this document of the "top 10" endoscopic advances of 2021.

A survey of colonoscopists with and without in-depth knowledge of water-aided colonoscopy.

BACKGROUND AND AIM: Endoscopy featured water-aided colonoscopy (WAC) as novel in the Innovation Forum in 2011. Gastrointestinal Endoscopy published a modified Delphi consensus review (MDCR) that supports WAC for clinical practice in 2021. We tested the hypothesis that experience was an important predictor of WAC use, either as water immersion (WI), water exchange (WE), or a combination of WI and WE. METHODS: A questionnaire was sent by email to the MDCR authors with an in-depth knowledge of WAC. They responded and also invited colleagues and trainees without in-depth knowledge to respond. Logistic regression analysis was used with the reasons for WAC use treated as the primary outcome. Reports related to WAC post MDCR were identified. RESULTS: Of 100 respondents, > 80% indicated willingness to adopt and modify practice to accommodate WAC. Higher adenoma detection rate (ADR) incentivized WE use. Procedure time slots ≤ 30 and > 30 min significantly predicted WI and WE use, respectively. Co-authors of the MDCR were significantly more likely to perform WAC (odds ratio [OR] = 7.5, P = 0.037). Unfamiliarity with (OR = 0.11, P = 0.02) and absence of good experience (OR = 0.019, P = 0.002) were associated with colonoscopists less likely to perform WAC. Reports related to WAC post MDCR revealed overall and right colon WE outcomes continued to improve. Network meta-analyses showed that WE was superior to Cap and Endocuff. On-demand sedation with WE shortened nursing recovery time. CONCLUSIONS: An important predictor of WAC use was experience. Superior outcomes continued to be reported with WE.

Evaluation of the vestibular/ocular motor screening assessment in active combat sport athletes: an exploratory study.

OBJECTIVE: The first aim of this study was to compare the results of the vestibular/ocular motor screening (VOMS) in combat sport athletes with a healthy control population. Second, to explore differences between athletes with and without a concussion history. Third, to examine the relationship between VOMS and the Post-Concussion Symptom Scale (PCSS) in combat sport athletes. PARTICIPANTS: Forty active male combat sport athletes and 40 healthy male control participants were recruited from 4 clubs and a University in Australia. METHODS: Participants completed the VOMS in a primary care physiotherapy clinic. Participants completed an injury questionnaire and the PCSS. RESULTS: An "abnormal" score in at least one subtest or near point convergence (NPC) was recorded in 45% of the combat group compared with 22.5% of the control group. All VOMS scores and NPC distance were greater in the combat group compared with control group (p < 0.05). The VOMS scores were found to be moderately positively correlated with the PCSS. There was no difference in VOMS between athletes with and without a history of concussion (p > 0.05). CONCLUSION: VOMS scores differed between combat sport athletes and control participants. The PCSS may aid clinicians in identifying athletes who have underlying vestibular/oculomotor impairment.

GIE Editorial Board top 10 topics: advances in GI endoscopy in 2020.

The American Society for Gastrointestinal Endoscopy's Gastrointestinal Endoscopy Editorial Board reviewed a systematic literature search of original endoscopy-related articles published during 2020 in Gastrointestinal Endoscopy and 10 other high-impact medical and gastroenterology journals. Votes from each individual board member were tallied to identify a consensus list of the 10 most significant topic areas in GI endoscopy over the calendar year of study using 4 criteria: significance, novelty, impact on national health, and impact on global health. The 10 areas identified were as follows: artificial intelligence in endoscopy, coronavirus disease 2019 and GI practice, third-space endoscopy, lumen-apposing metal stents, single-use duodenoscopes and other disposable equipment, endosonographic needle technology and techniques, endoscopic closure devices, advances in GI bleeding management, improvements in polypectomy techniques, and bariatric endoscopy. Each board member contributed a summary of important articles relevant to 1 to 2 topic areas, leading to a collective summary that is presented in this document of the "top 10" endoscopic advances of 2020.

Comparison of Right Colon Adenoma Miss Rates Between Water Exchange and Carbon Dioxide Insufflation: A Prospective Randomized Controlled Trial.

GOALS: To test the hypothesis that water exchange (WE), when compared with carbon dioxide (CO2) insufflation, significantly reduces the right colon adenoma miss rate (rAMR) in a blinded randomized controlled trial with cap-assisted colonoscopy. BACKGROUND: The unblinded consecutive group observational data showed that WE significantly decreased rAMR. The unblinded data are limited by potential bias. STUDY: Consecutive patients aged 45 years or more were randomized to undergo insertion with WE or CO2. Withdrawal and polypectomy were performed with CO2 in both groups to the hepatic flexure. The colonoscope was reinserted to the cecum. A second colonoscopist re-examined the right colon. The second colonoscopist was unaware, but made a guess, of the initial insertion method. The number of additional adenomas divided by the total number detected in both examinations equaled rAMR. RESULTS: Among 262 patients (131/group), demographic variables were similar. The body mass index was significantly higher in the WE group. Compared with CO2, WE significantly decreased rAMR [18.0% (33/183) vs. 34.6% (62/179), P=0.0025] and right colon serrated polyp miss rate [17.4% (27/155) vs. 39.3% (33/84), P=0.002]. Multivariate logistic regression analysis showed that WE was an independent predictor of rAMR (odds ratio, 0.42; 95% confidence interval, 0.21-0.86), and so was ≥2 adenomas in the right colon (odds ratio, 2.35; 95% confidence interval, 1.17-4.76). Whether the second colonoscopist guessed the insertion method correctly or not, and demographic and procedure variables were not associated with rAMR. CONCLUSIONS: The randomized controlled trial validated unblinded observational data showing that WE significantly decreased rAMR and right colon serrated polyp miss rate (clinical trial registration number: NCT03845933).

Heat sink effect of underwater polypectomy in a porcine colon model.

BACKGROUND: Underwater polypectomy without the need for submucosal injection has been reported. A heat-sink effect by immersing the polyp in water was proposed but no such experiment has been performed to support the claim. We compared the temperature rise on the serosal side during polypectomy between air- and water-filled colon. METHOD: Freshly harvested porcine colons were placed in a metal tray with cautery electrode pad attached to its bottom. An upper endoscope was used with a cap and a rubber band mounted to the distal end. A mucosal site was randomly selected and identified on its serosal surface with a marker while suction was applied. Suction was applied again and a ligation band was applied to create a polyp. A cautery snare grasped the artificial polyp just below the band. An assistant placed the tip of a thermometer at the marked site on the serosal surface to record the baseline temperature before cautery and the highest temperature during polypectomy. Seven polypectomies in air and underwater were performed. RESULTS: Mean (standard deviation) baseline temperature were 23.3 (0.6) °C and 23.4 (0.6) °C in the air and water groups, respectively. The maximum rise in temperature during polypectomy was 6.1 (4.5) °C and 1.4 (1.0) °C in the air and water groups, respectively (P = 0.004). CONCLUSIONS: The maximum temperature rise during polypectomy was significantly less when polypectomy was performed underwater, supporting the hypothesis that a heat-sink effect does exist during underwater polypectomy.

Sessile serrated adenoma/polyp detection rate of water exchange, Endocuff, and cap colonoscopy: A network meta-analysis.

BACKGROUND AND AIM: Sessile serrated adenoma/polyp (SSA/P) may contribute to interval cancer. In a recent meta-analysis, water exchange (WE) was shown to be superior to Endocuff and cap colonoscopy at adenoma and advanced adenoma detection. The strong positive correlation between adenoma detection rate (ADR), advanced adenoma detection rate (AADR), and sessile serrated adenoma/polyp detection rate (SSA/PDR) prompted us to hypothesize that WE could significantly improve SSA/PDR compared with Endocuff and cap colonoscopy. METHODS: The literature was searched for all randomized controlled trials (RCTs) that reported SSA/PDR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing SSA/PDR of each method using air insufflation as the control and reported the odds ratios (ORs) with 95% confidence interval (CI). Performances were ranked based on P-score. RESULTS: A total of 531 articles resulted from initial keywords search. Eleven RCTs were included in the analysis. A total of 7856 patients underwent air insufflation, WE, Endocuff, or cap colonoscopy. WE significantly increased SSA/PDR (OR 2.04; 95% CI 1.33-3.13). Endocuff (OR 1.15; 95% CI 0.94-1.41) and cap (OR 1.08; 95% CI 0.42-2.74) did not significantly impact SSA/P detection. P-scores for WE (0.96), Endocuff (0.49), cap (0.37), and air insufflation (0.17) suggested that WE had the highest SSA/PDR. The results did not change after adjusting for mean withdrawal time and indication for colonoscopy. CONCLUSION: Water exchange significantly increases SSA/PDR and is superior to Endocuff and cap colonoscopy at detecting SSA/P.

Adenoma and Advanced Adenoma Detection Rates of Water Exchange, Endocuff, and Cap Colonoscopy: A Network Meta-Analysis with Pooled Data of Randomized Controlled Trials.

BACKGROUND AND AIMS: A network meta-analysis showed that low-cost optimization of existing resources was as effective as distal add-on devices in increasing adenoma detection rate (ADR). We assessed the impacts of water exchange (WE), Endocuff, and cap colonoscopy on ADR and advanced adenoma detection rate (AADR). We hypothesized that WE may be superior at improving ADR and AADR. METHODS: The literature was searched for all randomized controlled trials (RCTs) that reported ADR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing ADR and AADR of each method using air insufflation (AI) as the control and reported the odds ratios with 95% confidence interval. Performances were ranked based on P-score. RESULTS: Twenty-one RCTs met inclusion criteria. Fourteen RCTs also reported AADR. Both WE [1.46 (1.20-1.76)] and Endocuff [1.39 (1.17-1.66)] significantly increase ADR, while cap has no impact on ADR [1.00 (0.82-1.22)]. P-scores for WE (0.88), Endocuff (0.79), cap (0.17), and AI (0.17) suggest WE has the highest ADR. WE [1.38 (1.12-1.70)], but not Endocuff [0.96 (0.76-1.21)] or cap [1.06 (0.85-1.32)], significantly increases AADR. P-scores for WE (0.98), cap (0.50), AI (0.31), and Endocuff (0.21) suggest WE is more effective at increasing AADR. The results did not change after adjusting for age, proportion of males, and withdrawal time. CONCLUSION: WE may be the modality of choice to maximally improve ADR and AADR.

The prevalence and burden of recurrent headache in Australian adolescents: findings from the longitudinal study of Australian children.

BACKGROUND: Headache disorders are highly prevalent worldwide, but not well investigated in adolescents. Few studies have included representative nationwide samples. This study aimed to present the prevalence and burden of recurrent headache in Australian adolescents. METHODS: The prevalence of recurrent headache, headache characteristics (severity and frequency) and burden on health-related quality of life in Australian children aged 10-17 years were presented, using nationally representative data from the Longitudinal Study of Australian children (LSAC). The LSAC, commencing in 2004, collects data every 2 years from a sample of Australian children of two different age cohorts: B 'baby' cohort, aged 0-1 years and K 'kindergarten' cohort, aged 4-5 years at the commencement of the study. Face-to-face interviews and self-complete questionnaires have been conducted with the study child and parents of the study child (carer-reported data) at each data collection wave, with seven waves of data available at the time of the current study. Wave 7 of the LSAC was conducted in 2016, with B cohort children aged 12-13 years and K cohort children aged 16-17 years. For the current study, data were accessed for four out of seven waves of available data (Wave 4-7) and presented cross-sectionally for the two cohorts of Australian children, for the included age groups (10-11 years, 12-13 years, 14-15 years and 16-17 years). All available carer-reported questionnaire data pertaining to headache prevalence, severity and frequency, general health and health-related quality of life, for the two cohorts, were included in the study, and presented for male and female adolescents. Carer-reported general health status of the study child and health-related quality of life scores, using the parent proxy-report of the Paediatric Quality of Life Inventory™ 4.0, were compared for male and female adolescents with recurrent headache and compared with a healthy group. Finally, health-related quality of life scores were compared based on headache frequency and severity. RESULTS: The LSAC study initially recruited 10,090 Australian children (B cohort n = 5107, K cohort n = 4983), and 64.1% of the initial sample responded at wave 7. Attrition rates across the included waves ranged from 26.3% to 33.8% (wave 6 and 7) for the B cohort, and 16.3% to 38.0% (wave 4-7) for the K cohort. Recurrent headache was more common in females, increasing from 6.6% in 10-11 years old females to 13.2% in 16-17 years old females. The prevalence of headache in males ranged from 4.3% to 6.4% across the age groups. Health-related quality of life scores were lower for all functional domains in adolescents with recurrent headache, for both sexes. Headache frequency, but not severity, was significantly associated with lower health-related quality of life scores, in both males and females. CONCLUSIONS: Recurrent headache was common among Australian adolescents and increased in prevalence for females, across the age groups. Frequent recurrent headache is burdensome for both male and female adolescents. This study provides information regarding the prevalence and burden of recurrent headache in the adolescent population based on findings from the Longitudinal Study of Australian Children.