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Background: Adherence-to-colonoscopy in cascade screening of colorectal cancer (CRC) is crucial to the effectiveness of screening, but it has not been systematically evaluated. We aimed to evaluate the colonoscopy adherence among average-risk populations globally. Methods: We searched Pubmed, Embase, Web of Science, and Cochrane Library for observational and experimental studies published in English up to December 31, 2018 and reporting the colonoscopy adherence following positive initial screening. We calculated pooled adherence with its 95% confidence intervals (CIs) using a random-effects meta-analysis. Subgroup and mixed-effects meta-regression analysis were performed to evaluate heterogeneous factors for adherence. Findings: Of 9,772 articles identified, 191 (313 studies) were included in the systematic review. The pooled adherence-to-colonoscopy was 81·6% (95% CI: 79·6-83·4), with the estimates varying substantially by continents, CRC incidence, GDP per capita, recruitment method, screening round and type of initial test. Type of initial test was the most modifiable heterogeneous factor for adherence across studies (Q=53·00, P

Little is known regarding the health effects of different hypertension phenotypes including isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic and diastolic hypertension (SDH) defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline among young adults. We conducted this longitudinal study using time-varying analyses to evaluate the relationship between cardiovascular/all-natural mortality risk and different hypertension phenotypes in young adults.A total of 284 597 young adults (aged 18-39 years) were recruited between 1996 and 2016. Participants were classified into eight mutually exclusive BP groups: normal blood pressure (BP), elevated BP, stage 1 IDH, stage 1 ISH, stage 1 SDH, stage 2 IDH, stage 2 ISH, and stage 2 SDH. The outcomes were cardiovascular and all-natural mortality.After a median follow-up of 15.8 years, 2341 all-natural deaths with 442 cardiovascular deaths were observed. When compared with individuals with normal BP, the multivariable adjusted hazard ratios (95% confidence interval) of cardiovascular mortality was 1.39 (1.01-1.93) for elevated BP, 2.00 (1.45-2.77) for stage 1 IDH, 1.66 (1.08-2.56) for stage 1 ISH, 3.08 (2.13-4.45) for stage 1 SDH, 2.85 (1.76-4.62) for stage 2 IDH, 4.30 (2.96-6.25) for stage 2 ISH, and 6.93 (4.99-9.61) for stage 2 SDH, respectively. In consideration to all-natural mortality, similar results were observed for stage 1 SDH, stage 2 ISH, and stage 2 SDH; but not for elevated BP, stage 1 IDH, stage 1 ISH, and stage 2 IDH.Young adults with stage 1 or stage 2 ISH, IDH, and SDH are at increased risk of cardiovascular death than those with normal BP. Regardless of BP stage, SDH was associated with a higher cardiovascular mortality risk than IDH and ISH.

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.

Background and aim The reported prevalence and risk factors for sessile serrated lesions (SSLs) show significant variation. We aimed to specifically study the prevalence and potential risk factors of SSLs in an average risk colorectal cancer (CRC) screening population of Chinese subjects. Methods This is a case-control study of prospectively collected data from a territory-wide colorectal screening program in Hong Kong. Information on risk factors was obtained from questionnaires completed prior to screening colonoscopy. We compared subjects with SSLs against controls without these lesions to identify potential risk factors using multivariable logistic regression. Results Of 12 039 asymptomatic screening subjects, 6011 subjects received a screening colonoscopy with 2214 subjects (36.8%) having conventional adenomas, 486 subjects (8.1%) having hyperplastic polyps, and 85 subjects (1.4%) having SSLs only. Of these subjects, three had synchronous advanced adenomas and were excluded from the analysis. More than 60% of these lesions were in the proximal colon. We compared these 82 subjects with SSLs only and 3226 controls without any polyps. After multivariable logistic regression, age ≥ 66 years, smoking, and diabetes mellitus (DM) were significant independent risk factors for SSLs. Conclusion In this study, we report the prevalence of SSLs to be 1.4%. Age ≥ 66 years, smoking, and DM were independent risk factors for these lesions. Our findings provide relevant new data that should be taken into consideration when designing region-specific surveillance programs for SSLs with the ultimate goal of reducing the risk of CRC.

A quality of life assessment is useful in identifying a specific health impact on patients who are suffering from various medical conditions. This study estimated the quality of life among patients with cancers of the lungs, breast, colorectum, oesophagus, liver, and stomach in urban China and evaluates the associated factors. This study employed a random cluster sampling strategy to recruit patients with lung, breast, colorectal, oesophageal, liver, or stomach cancer from eleven third-grade class-A (the highest level) hospitals in Beijing between October 2013 and May 2014. We performed a quality of life survey that included solicitation of sociodemographic and clinical information and the use of a EuroQoL five-dimension three-level questionnaire. We applied the Chinese time trade-off method to calculate the health utility values, which were transformed into binary variables (using the median as the cut-off). In addition, multivariable logistic regression analysis was used to examine the factors associated with the quality of life. A total of 637 patients (91 with lung cancer, 152 with breast cancer, 60 with colorectal cancer, 108 with oesophageal cancer, 154 with liver cancer, and 72 with stomach cancer) were included in this study; the medians of the health utility values were 0.780, 0.800, 0.800, 0.860, 0.800, and 0.870, respectively. The most common concerns for patients of all six cancer types were pain/discomfort and anxiety/depression. The reported health status of patients was associated with various demographic and clinical variables. This study highlighted that pain relief and psychological support are important aspects of patient management for those with these types of cancer. Individuals with factors associated with a poorer quality of life should be targets for additional support.

Background Prostate-specific antigen (PSA) and prostate health index (PHI) have been used as biomarkers for prostate cancer detection. In this study, we aimed to evaluate the cost-effectiveness of PHI for prostate cancer detection in Chinese men. Method We developed a Markov model for Chinese male patient aged 50-75 years old. The PSA strategy was to offer TRUS-PB for all patients with elevated PSA of 4-10 ng/mL. The PHI strategy was to offer PHI for patients with elevated PSA of 4-10 ng/mL. TRUS-PB would only be offered for patients with PHI >35.0. Model inputs were extracted from local data when available. The cost per quality-adjusted life years gained for both strategies were calculated. The incremental cost-effectiveness ratios in relation to the willingness-to-pay (WTP) threshold were compared. One-way sensitivity analysis and probabilistic sensitivity analysis were performed. Cost-effectiveness acceptability curves were also constructed. Results With a Markov model of 25 screening cycles from age 50 to 75 years, the mean total costs per man were estimated to be USD 27,439 in the PSA strategy and USD 22,877 in the PHI strategy. The estimated effects were estimated to be 15.70 in the PSA strategy and 16.05 in the PHI strategy. The PHI strategy was associated with an expected decrease in cost of USD 4562 and an expected gain of 0.35 QALY, resulting in an ICER of USD -13056.56. The results were shown to be robust upon one-way sensitivity analysis. Upon Monte Carlo simulation, the PHI strategy was more cost-effective for 100% of the iterations. The PHI strategy demonstrated dominance over the PSA strategy regardless of what WTP threshold we use. Conclusions A PHI-based screening strategy may be more cost-effective than a PSA-based strategy for prostate cancer detection in Chinese men. These results support consideration of a PHI-based approach for prostate cancer in Hong Kong.

Background Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. Methods This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). Results We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. Conclusions Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.

Background To evaluate the long-term association between organised colorectal cancer (CRC) screening and reduction of CRC-related mortality. Methods We systematically reviewed studies on organized CRC screening through PubMed, Ovid Medline, Embase and Cochrane database from its inception to November 2020. Moreover, we retrieved the matched CRC-related mortality (over 50 years) of those areas from the initial year of CRC screening programmes to the latest data available obtained from the International Agency for Research on Cancer (IARC). The mortality in the initial year and the latest year was used to calculate the age-standardised mortality ratio (ASMR). We adopted a random-effects model to synthesis the ASMR. Subgroup analyses were performed according to the screening period and modalities. Furthermore, a linear mixed model (LMM) was conducted as a sensitivity analysis. Results CRC screening programmes have been conducted in 58 countries/regions. After matching with the IARC database, we recorded >2.5 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The screening modality with a provision of choice between faecal tests and colonoscopy as the primary screening test was associated with a 38.1% reduction in CRC mortality (ASMR=0.619, 95%CI: 0.549-0.698), which was higher than programmes that offered guaiac faecal occult blood test (gFOBT) (0.894, 0.835-0.958), faecal immunochemical tests (FIT) (0.879, 0.847-0.913), gFOBT or FIT (0.882, 0.835-0.932), and faecal tests or flexible sigmoidoscopy (0.840, 0.786-0.898). The longer duration of screening was associated with a higher reduction in the pooled ASMR. In particular, the pooled ASMR became non-significant (0.987, 0.934-1.043) when the FIT screening was implemented for less than 5 years (IDDF2021-ABS-0179 Figure 1. The pooled age-standardised colorectal cancer-related mortality ratio by screening modalities and screening duration). The LMM result also showed a 0.172 decrease in ASMR (P Conclusions A CRC screening programme running for >5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised CRC screening providing a choice between faecal tests and colonoscopy as a preferred primary screening test.

ObjectivesAnimal experiments indicate that exposure to particulate matter (PM) can induce hepatotoxic effects but epidemiological evidence is scarce. We aimed to investigate the associations between long-term exposure to PM air pollution and liver enzymes, which are biomarkers widely used for liver function assessment.MethodsA cross-sectional analysis was performed among 351 852 adult participants (mean age: 40.1 years) who participated in a standard medical screening programme in Taiwan. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) levels were measured. A satellite-based spatio-temporal model was used to estimate the concentrations of ambient fine particles (PM with an aerodynamic diameter ≤2.5 µm, PM2.5) at each participant’s address. Linear and logistic regression models were used to investigate the associations between PM2.5 and the liver enzymes with adjustment for a wide range of potential confounders.ResultsAfter adjustment for confounders, every 10 µg/m3 increment in 2-year average PM2.5 concentration was associated with 0.02%(95% CI: −0.04% to 0.08%), 0.61% (95% CI: 0.51% to 0.70%) and 1.60% (95% CI: 1.50% to 1.70%) increases in AST, ALT and GGT levels, respectively. Consistently, the odds ratios of having elevated liver enzymes (>40 IU/L) per 10 µg/m3 PM2.5 increment were 1.06 (95% CI: 1.04 to 1.09), 1.09 (95% CI: 1.07 to 1.10) and 1.09 (95% CI: 1.07 to 1.11) for AST, ALT and GGT, respectively.ConclusionsLong-term exposure to PM2.5 was associated with increased levels of liver enzymes, especially ALT and GGT. More studies are needed to confirm our findings and to elucidate the underlying mechanisms.

OBJECTIVES: To assess the risk of coronavirus transmission to healthcare workers performing aerosol-generating procedures and the potential benefits of personal protective equipment during these procedures. DATA SOURCES: MEDLINE, EMBASE, and Cochrane CENTRAL were searched using a combination of related MeSH terms and keywords. STUDY SELECTION: Cohort studies and case controls investigating common anesthetic and critical care aerosol-generating procedures and transmission of severe acute respiratory syndrome coronavirus 1, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2 to healthcare workers were included for quantitative analysis. DATA EXTRACTION: Qualitative and quantitative data on the transmission of severe acute respiratory syndrome coronavirus 1, severe acute respiratory syndrome coronavirus 2, and Middle East respiratory syndrome coronavirus to healthcare workers via aerosol-generating procedures in anesthesia and critical care were collected independently. The Risk Of Bias In Non-randomized Studies - of Interventions tool was used to assess the risk of bias of included studies. DATA SYNTHESIS: Seventeen studies out of 2,676 yielded records were included for meta-analyses. Endotracheal intubation (odds ratio, 6.69, 95% CI, 3.81-11.72; p < 0.001), noninvasive ventilation (odds ratio, 3.65; 95% CI, 1.86-7.19; p < 0.001), and administration of nebulized medications (odds ratio, 10.03; 95% CI, 1.98-50.69; p = 0.005) were found to increase the odds of healthcare workers contracting severe acute respiratory syndrome coronavirus 1 or severe acute respiratory syndrome coronavirus 2. The use of N95 masks (odds ratio, 0.11; 95% CI, 0.03-0.39; p < 0.001), gowns (odds ratio, 0.59; 95% CI, 0.48-0.73; p < 0.001), and gloves (odds ratio, 0.39; 95% CI, 0.29-0.53; p < 0.001) were found to be significantly protective of healthcare workers from contracting severe acute respiratory syndrome coronavirus 1 or severe acute respiratory syndrome coronavirus 2. CONCLUSIONS: Specific aerosol-generating procedures are high risk for the transmission of severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2 from patients to healthcare workers. Personal protective equipment reduce the odds of contracting severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2.

Background: Sessile serrated adenoma/polyp is notorious for its malignancy potential and the difficulty to be detected and distinguished under endoscopy. This systematic review and meta-analysis aimed to evaluate endoscopic characteristics of SSA/P and delineate features that inform distinction between SSA/P and other types of lesions, including hyperplasitc polyp (HP) and conventional adenoma. Methods: MEDLINE, Embase and Cochrane Library from the inception to September 9, 2020 were searched for cohort, cross-sectional or case-control studies comparing endoscopic characteristics of SSA/P and other polyps. The primary outcome measure was the odds of finding specific endoscopic characteristics in patients with SSA/P compared with other types of polys in patients undergoing colorectal cancer screening. Findings: We included 74 studies from 16 countries comprising 34,535 SSA/P. Compared with HP, SSA/P was more likely to be in the right colon (OR 5.45; 95% CI 4.13-7.17; P 5mm vs.

Background: Asymptomatic infection of SARS-CoV-2 may lead to silent community transmission and compromise pandemic control measures of COVID-19. We aimed to estimate the rate of asymptomatic COVID-19 infection from published studies, and compare this rate among different patient groups. Methods: The electronic databases including Medline, Embase, PubMed, and three Chinese electronic databases (The Chinese National Knowledge Infrastructure (CNKI), WanFang Data, and VIP) were searched. Studies with sample size (or number of subjects) not less than 5 were included. The STATA command ‘Metaprop’ was implemented to conduct meta-analysis for the pooled rate estimates of asymptomatic infections with exact binomial and score test-based 95% confidence intervals (CIs). Results: A total of 12,713 COVID-19 patients in 136 studies were included in the meta-analysis, including 2,785 asymptomatic infections. The overall rate of asymptomatic infection was 15.1% (95% CI: 12.0%-18.4%). Subgroup analysis showed that the rate was significantly higher in pregnant women (36.3%, 95% CI: 15.7%-59.6%), children (29.4%, 17.4%-42.9%), and studies for screening settings (25.3%, 15.4%-36.5%) conducted on or after 01 March 2020 (27.8%, 15.7%-41.7%). In terms of geographical regions, the rate was the highest in Asia (excluding China) (27.4%, 14.3%-42.6%), followed by Europe (22.7%, 6.3%-44.9%), the US (15.9%, 8.9%-24.3%), and China (13.1%, 10.2%-16.3%). Conclusions: High proportion of asymptomatic infection were observed in pregnant women, children, European residents, screening programmes, and in studies conducted in and after March 2020. Our findings help inform the true burden of COVID-19 among different groups of cases, and provide information on cost-effective strategies of identifying and tracing asymptomatic infections.

Background The success of population-based colorectal cancer (CRC) screening is dependent on the optimal achievement of various targets. We estimated the pooled performance indicators of CRC screening programmes that used faecal immunochemical tests (FIT) as a primary screening modality and colonoscopy as a subsequent confirmatory test in various countries. Methods We searched PubMed, Ovid MEDLINE, Embase, and Cochrane from inception to 1st Jan 2020. We included original articles published in the English language describing population-based CRC screening programme that used FIT and colonoscopy, and relevant national CRC screening reports by hand searching. We extracted data to pool early performance indicators, including participation rate, invalid FIT rate, FIT positive rate, adenoma/CRC detection rate of FIT, colonoscopy compliance rate, rate of adequate bowel preparation, colonoscopy completion rate, colonoscopy complication rate, and positive predictive values (PPV) of FIT for adenoma/CRC. We used Metaprop to conduct a meta-analysis via R software (version 3.6.3). The Freeman-Tukey double arcsine transformation was used to stabilise the variances, and a random-effects model was used to pool the rates with proportions. Results A total of 85 studies (64 articles and 21 reports) were included in this meta-analysis. The pooled participation rate was 52.2%, and the pooled proportion of invalid FIT was 1.0%. The FIT positive rate was 7.0%, the adenoma detection rate was 21.8‰, and the CRC detection rate was 2.5‰. In addition, the colonoscopy compliance rate (79.1%), rate of adequate bowel preparation (86.3%), and the colonoscopy completion rate (93.1%) were high. We found the pooled complication rate of 0.3%, with PPVs of FIT being 39.2% (for adenoma) and 4.7% (for CRC). The range of all indicators varied substantially. In subgroup analysis, a higher FIT cut-off value indicated lower positivity and lower adenoma detection rate. Compared with CRC screening programmes with one FIT, those with two FIT had lower participation rate (48.8% vs 55.5%) but higher positive rate (8.9% vs 5.8%) and adenoma detection rate (21.8‰ vs 17.3‰). Conclusions Our findings reported the pooled performance indicators of different CRC screening programmes. The summary measures could inform the benchmarking of performance indicator targets across different CRC screening programmes.

Background Worldwide, oesophageal cancer is one of the most common cancers and a leading cause of cancer mortality. Owing to its aggressive disease nature and poor survival rate, it contributes to a substantial burden to global health and clinical practice. This study aimed to estimate the worldwide incidence and risk factors of oesophageal cancer by histological subtypes using data from 178 countries. Methods The data on the incidence of oesophageal cancer by histological types in 2018 were estimated from GLOBALCAN and Cancer Incidence in Five Continents (CI5). Age-standardized rates (ASRs) for oesophageal cancer incidence by histological subtypes were evaluated by Segi–Doll population. The prevalence of tobacco use, alcohol drinking, physical inactivity, obesity, diabetes, and lipid disorders for each country were retrieved from the Global Health Observatory. The association between the ratio of histological subtypes and risk factors was examined by multivariable linear regression. Results We estimated a total of 63,470 (12.6%) and 502,669 new cases of oesophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) in 2018, respectively. The incidence among males was 3.6-fold and 2.2-fold of that among females for AC and SCC, respectively. The highest AC:SCC ratio was found in the UK (ratio 2.880, ASR 7.5), New Zealand (2.667, 4.2), the Netherlands (2.536, 7.7), Bahrain (2.143, 0.9), and Canada (2.000, 3.7) among males (figure 1). As for females, the highest AC:SCC ratio was observed in Moldova (1.000, 0.2), the Netherlands (0.800, 1.2), Iceland (0.750; 0.5), the UK (0.700; 1.4), and Cyprus (0.667; 0.3). A higher AC:SCC ratio was associated with a higher prevalence of obesity (male: β 0.039, 95% CI 0.023 to 0.055; female: 0.009, 0.004 to 0.146) and high cholesterol (male: 0.028, 0.010 to 0.047; female: 0.011, 0.004 to 0.019); but a lower prevalence of tobacco use (male: -0.007, -0.014 to -0.001) and diabetes (male: 0.009, 0.004 to 0.146; female: -0.021, -0.038 to -0.003). Conclusions While SCC is the predominant subtype of oesophageal cancer, the incidence of AC has surpassed SCC in a substantial proportion of countries, probably due to the increasing prevalence of obesity and metabolic disorders. Future research should investigate the reasons behind these epidemiological changes.

ObjectiveThe association between the regular use of proton pump inhibitors (PPIs) and the risk of type 2 diabetes remains unclear, although a recent randomised controlled trial showed a trend towards increased risk. This study was undertaken to evaluate the regular use of PPIs and risk of type 2 diabetes.MethodThis is a prospective analysis of 204 689 participants free of diabetes in the Nurses' Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS). Type 2 diabetes was confirmed using American Diabetes Association (ADA) diagnostic criteria. We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications and clinical indications.ResultsWe documented 10 105 incident cases of diabetes over 2 127 471 person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than non-users (HR 1.24, 95% CI 1.17 to 1.31). The risk of diabetes increased with duration of PPI use. Fully adjusted HRs were 1.05 (95% CI 0.93 to 1.19) for participants who used PPIs for >0–2 years and 1.26 (95% CI 1.18 to 1.35) for participants who used PPIs for >2 years compared with non-users.ConclusionsRegular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use. Physicians should therefore exercise caution when prescribing PPIs, particularly for long-term use.

Background Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain. Methods We performed a prospective study in 2 regional hospitals in Hong Kong. Results We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% [sputum] and 80.9% [pooled NP and throat swabs]) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62–0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum. Conclusions Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.

Highlights • We examined the detection rate of SARS-CoV-2 RNA in specimens of COVID-19 patients. • The pooled detection rate of the RNA was 43.7% (by patient) and 33.7% by specimens. • Female patients, those with symptoms or more severe disease had higher detection rate. • Infection control strategies on fecal spread and contamination are urgently needed., Introduction Recent studies showed that SARS-CoV-2 RNA may be found in fecal specimens of COVID-19 patients, but the sample size is limited. This systematic review and meta-analysis examined the detection rate of SARS-CoV-2 RNA in fecal specimens of these patients according to their clinical characteristics. Methods MEDLINE, Embase, Scopus, and three Chinese biomedical databases were searched up to 25 March 2020 with no language restriction. We included original observational studies that reported the detection rate of SARS-CoV-2 RNA in fecal specimens of COVID-19 patients. Two separate reviewers conducted the review. Metaprop was adopted to conduct a meta-analysis of prevalence with variances stabilized by Freeman-Tukey Double Arcsine Transformation. A random-effects model was used. Heterogeneity across different studies was computed using Cochran's Q test and chi square statistics. Results From 17 studies, the pooled detection rate of fecal SARS-CoV-2 RNA was 43.7% (95% CI 32.6%-55.0%) and 33.7% (95% C.I. 33.7%, 95% C.I. 20.1%-48.8%) by patient and number of specimens as a unit count, respectively. Female individuals (59.6% vs. 53.5%), those who presented with gastrointestinal symptoms (77.1% vs. 57.7%), and patients with more severe disease (68.3% vs. 34.6%) tended to have a higher detection rate. Discussion A significant proportion of COVID-19 patients carry SARS-CoV-2 in their intestinal tract. Feces being a self-collected specimen bears a potential to improve case identification in community, especially for young children where proper respiratory sampling at home is difficult. Specific infection control strategies focusing on spread via fecal contamination and faulty toilet drainage are urgently needed.

Patients with hypertension may develop a thoracic aortic aneurysm (TAA) that can be asymptomatic but potentially life-threatening. We sought to assess the prevalence of asymptomatic TAA among hypertensive patients with a point-of-care screening program using pocket-size mobile echocardiographic (PME) devices.We prospectively performed transthoracic aortic ultrasound using a PME device on patients attending our hypertension clinics between June 2016 and July 2018. The echo examinations were performed by a research fellow to obtain aortic diameter measurements including the aortic sinus, sinotubular junction, ascending aorta, aortic arch, and descending thoracic aorta through various standard echo views. Images were stored on the PME and transferred to a desktop computer for measurements and further statistical analysis.During the study period 1529 hypertensive patients (mean age, 62 years [range, 30-85]; 824 men) were recruited. The prevalence of TAA (defined as maximum aortic diameter ≥ 4.5 cm and/or50% larger than the diameter of the adjacent normal aorta) in our study population was 7.5% (115/1529). Multiple logistic regression analysis identified male gender (odds ratio, 2.120; P.001) and older age (odds ratio, 1.031; P.001) as independent factors associated with TAA.Silent TAA is common among hypertensive patients in Hong Kong. We found the PME device to be effective in detecting TAA in a clinic setting. Such an approach may be useful for early detection of TAA among at-risk patients, allowing aggressive blood pressure control and early surgical intervention to prevent catastrophic complications.

OBJECTIVE This study aimed to evaluate the incidence of and factors associated with persistence and clearance of oral human papillomavirus (HPV) infections. METHOD A prospective cohort study invited 458 subjects (231 HPV-positive and 227 HPV-negative at baseline) to attend follow-ups at 12 months. Those 231 HPV-positive subjects and 10 new infections were invited to reassessment at 24 months. We used next-gen sequencing for detection and genotyping of HPV. RESULTS α-HPV infections showed higher persistence rates than β/γ-HPV (22.7% vs 9.2% at 12 months [P

Background Brugada syndrome is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF), potentially leading to sudden cardiac death (SCD). Tpeak-Tend intervals, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion have been proposed for risk stratification, but their predictive values in Brugada syndrome have been challenged recently. Methods A systematic review and meta-analysis was conducted to examine their values in predicting arrhythmic and mortality outcomes in Brugada Syndrome. PubMed and Embase databases were searched until 1 May 2018, identifying 29 and 57 studies. Results Nine studies involving 1740 subjects (mean age 45 years old, 80% male, mean follow-up duration was 68 ± 27 months) were included. The mean Tpeak-Tend interval was 98.9 ms (95% CI: 90.5-107.2 ms) for patients with adverse events (ventricular arrhythmias or SCD) compared to 87.7 ms (95% CI: 80.5-94.9 ms) for those without such events, with a mean difference of 11.9 ms (95% CI: 3.6-20.2 ms, P = 0.005; I 2 = 86%). Higher (Tpeak-Tend)/QT ratios (mean difference = 0.019, 95% CI: 0.003-0.036, P = 0.024; I 2 = 74%) and Tpeak-Tend dispersion (mean difference = 7.8 ms, 95% CI: 2.1-13.4 ms, P = 0.007; I 2 = 80%) were observed for the event-positive group. Conclusion Tpeak-Tend interval, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion were higher in high-risk than low-risk Brugada subjects, and thus offer incremental value for risk stratification.

Background and Aim: A proper colonoscopy referral criterion is essential for flexible sigmoidoscopy‐based colorectal cancer screening. We aimed to compare the predictive capability of four existing criteria to detect proximal neoplasia (PN) and advanced proximal neoplasia (APN) in a Chinese population. Methods: Asymptomatic Chinese participants aged 50–75 years, who received screening colonoscopy, were consecutively recruited. The four criteria included (i) UK flexible sigmoidoscopy; (ii) Italian Screening for COlon REctum; (iii) NORwegian Colorectal Cancer Prevention trial; and (iv) US clinical index. The sensitivity, specificity, positive/negative predictive value, and the number of subjects needed to screen (NNS)/refer (NNR) to detect one APN/PN were examined. The area under receiver operating characteristic curve was evaluated. Results: Among 5833 subjects, 749 (12.8%) and 151 (2.6%) cases were found to have PN and APN, respectively. US criteria achieved the highest sensitivity for PN (49%) and APN (66%), while UK criteria attained the highest specificity (93%) for PN/APN. The lowest NNS was required by US criteria for PN (16 vs 19–38) and APN (58 vs 69–86), while the lowest NNR was required by UK criteria for PN (3.2 vs 4.0–4.8) and APN (7 vs 10–16). The receiver operating characteristic of all four criteria was 0.57–0.61 for PN and 0.68–0.70 for APN. Conclusions: Among all the four criteria, US criteria had the highest sensitivity and lowest NNS, while UK criteria achieved the highest specificity and lowest NNR. Their limited discriminatory capability highlighted the need for a new score to predict PN/APN in Chinese populations.

The objective of this study is to evaluate if nurse-led repeated prescription (NRP) could ensure non-inferior disease control and would be accepted in Chinese patients with controlled hypertension (HT) in primary care clinics. A 12-month follow-up non-inferiority randomized trial was conducted. The non-inferior margins for systolic and diastolic blood pressure were 6.6 mmHg and 3.7 mmHg, respectively. Eligible patients (>18 years of age) with HT were randomized to the NRP and usual care (UC) groups for their regular clinical follow-up. We used ANCOVA to study the difference-of-difference of the blood pressures between the two groups. The levels of patient acceptance and experience of NRP were assessed by the observed opt-out rate and a qualitative analysis. We found no statistically significant differences in BP blood pressure between the NRP (N = 194) and UC (N = 199) groups. Only 4 of the participants in the NRP group opted out due to a preference for assessment by a physician. The interviewed participants (N = 12) felt positive about NRP, because they experienced more relaxed communication with the nurse and believed that the eligibility to join the NRP program was an indication of optimal BP control. We observed no adverse events. The findings show that NRP was well accepted and found to be non-inferior to physician consultation for HT management.

AIMS Previous trials on the effectiveness of genotype-guided warfarin dosing vs. conventional dosing have been inconclusive. We conducted a systematic review and meta-analysis of randomized trials comparing genotype-guided to conventional dosing strategies. METHODS PubMed and the Cochrane Library were searched up to 23 October 2017. RESULTS A total of 76 and 94 entries were retrieved were retrieved from PubMed and the Cochrane Library, respectively. A total of 2626 subjects in the genotype-guided dosing (mean age 63.3 ± 5.8 years; 46% male) and 2604 subjects in the conventional dosing (mean age 64.7 ± 6.1 years; 46% male) groups (mean follow-up duration 64 days) from 18 trials were included. Compared with conventional dosing, genotype-guided dosing significantly shortened the time to first therapeutic international normalized ratio (INR) (mean difference 2.6 days, standard error 0.3 days; P < 0.0001; I2 0%) and time to first stable INR (mean difference 5.9 days, standard error 2.0 days; P < 0.01; I2 94%). Genotype-guided dosing also increased the time in therapeutic range (mean difference 3.1%, standard error 1.2%; P < 0.01; I2 80%) and reduced the risks of both excessive anticoagulation, defined as INR ≥4 [risk ratio (RR) 0.87; 95% confidence interval (CI) 0.78, 0.98; P < 0.05; I2 : 0%), and bleeding (RR 0.82; 95% CI 0.69, 0.98; P < 0.05; I2 31%). No difference in thromboembolism (RR 0.84; 95% CI 0.56, 1.26; P = 0.40; I2 0%) or mortality (RR 1.16; 95% CI 0.46, 2.91; P = 0.76; I2 0%) was observed between the two groups. CONCLUSIONS Genotype-guided warfarin dosing offers better safety with less bleeding compared with conventional dosing strategies. No significant benefit on thromboembolism or mortality was evident.

Background Fibroblast growth factor 21 is a signalling protein involved in cell differentiation, morphogenesis, proliferation and metabolism. Recent studies have associated increased levels of FGF21 in the development of cardiovascular diseases, whereas others have reported no significant associations. Therefore, this systematic review and meta-analysis evaluated the value in predicting the risk of cardio-metabolic disorders and mortality. Methods PubMed and EMBASE were searched until 5th September 2017 for studies that evaluated the roles of FGF21 levels in cardio-metabolic disorders. Results A total of 183 and 301 entries were retrieved; 24 studies met the inclusion criteria. Four studies were identified by an additional search. Therefore, 28 studies were included in the final meta-analysis. High FGF21 levels significantly predicted the incidence of coronary artery disease (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.06–1.55; P Conclusion FGF21 significantly predicts the incidence of coronary artery disease, the risks of metabolic syndrome, diabetes mellitus and renal progression in diabetes. It also predicted all-cause and cardiovascular mortality.

Background and objectives Congenital long QT syndrome (LQTS) predisposes affected individuals to ventricular tachycardia/fibrillation (VF/VF), potentially resulting in sudden cardiac death. The Tpeak–Tend interval and the Tpeak–Tend/QT ratio, electrocardiographic markers of dispersion of ventricular repolarization, were proposed for risk stratification but their predictive values in LQTS have been controversial. A systematic review and meta-analysis was conducted to examine the value of Tpeak–Tend intervals and Tpeak–Tend/QT ratios in predicting arrhythmic and mortality outcomes in congenital LQTS. Method PubMed and Embase databases were searched until 9th May 2017, identifying 199 studies. Results Five studies on long QT syndrome were included in the final meta-analysis. Tpeak–Tend intervals were longer (mean difference [MD]: 13 ms, standard error [SE]: 4 ms, P = 0.002; I2 = 34%) in congenital LQTS patients with adverse events [syncope, ventricular arrhythmias or sudden cardiac death] compared to LQTS patients without such events. By contrast, Tpeak–Tend/QT ratios were not significantly different between the two groups (MD: 0.02, SE: 0.02, P = 0.26; I2 = 0%). Conclusion This meta-analysis showed that Tpeak–Tend interval is significant higher in individuals who are at elevated risk of adverse events in congenital LQTS, offering incremental value for risk stratification.

Impact of percutaneous coronary interventions (PCI) on health-related quality of life (HRQOL) is important but under-reported in elderly patients.To evaluate long-term health status in elderly patients who underwent PCI.Consecutive patients who underwent PCI at a university-affiliated hospital from September 2009 to June 2012 were prospectively enrolled with HRQOL assessment at baseline (up to 2 weeks before PCI) and at 6-, 12-, and 36-month follow-up using the EuroQol five-dimensional questionnaire descriptive profile and visual analogue scale (VAS). Minimally important benefit (MIB) in HRQOL was defined as greater than half an SD improvement in the baseline VAS score.Of 1957 patients, 49.9%, 29.1%, and 21.0% were aged younger than 65 years, 65 to 74 years, and 75 years and older, respectively. Mean VAS scores at baseline (50.1 ± 20.5 vs. 51.6 ± 20.5 vs. 52.6 ± 21.8; P = 0.09) and at 36 months (72.9 ± 14.0 vs. 72.8 ± 16.1 vs. 72.0 ± 14.8; P = 0.77) were similar between the three age groups, respectively. MIB at 36 months was observed in 65.7%, 61.9%, and 61.2% of patients in each age group, respectively. Proportion of patients aged 75 years and older reporting problems in pain/discomfort and self-care reduced from 91.2% and 24.8% at baseline to 41.4% and 10.1% at 36 months, respectively (both P0.01). Independent predictors of MIB in HRQOL at 36 months in patients 75 years and older included poor baseline HRQOL, MIB at 6 months, and presentation with myocardial infarction (all P0.01).Elderly patients experienced sustained long-term improvement in quality of life comparable with younger patients after PCI. Our findings suggest that age per se should not deter against revascularization because of sustained benefit in HRQOL.

From this population-based study of a Chinese general population, it was found that smoking, drinking, oral sex, and more sexual partners were associated with alpha human papillomavirus (HPV) infection of the oral cavity. Teeth brushing before sleep was protective for beta/gamma-HPVs., Background Knowledge of the prevalence of and risk factors for oral human papillomavirus (HPV) infection, especially cutaneous types, is limited. Methods A population-based study using next-generation sequencing consecutively recruited asymptomatic individuals aged 18–64 years from a proportional sampling of the general population of Hong Kong, according to age groups, gender, and regions of residence. We examined associations of alpha-, beta-, and gamma-HPVs from oral rinse samples with participants’ sociodemographics by logistic regression models. Results The prevalence of oral HPV infection among 1426 ethnic Chinese was 15.5% (95% confidence interval [CI], 13.7%–17.5%), 2.5% (95% CI, 1.8%–3.5%), 11.9% (95% CI, 10.3%–13.6%), and 2.9% (95% CI, 2.1%–3.9%) for any type, alpha-, beta-, and gamma-HPV, respectively. Prevalence of any high-risk HPV was 0.8% (95% CI, 0.4%–1.4%), and that of HPV-16 was 0.4% (95% CI, 0.2%–0.8%). HPV-8 and HPV-98 were the most common beta types detected, while HPV-4 and HPV-SD2R were the most common gamma types. Prevalence of alpha- and beta/gamma-HPV infection showed a similar pattern of increase with age, and was higher in men than women. Smoking, drinking, oral sex, and more sexual partners were associated with alpha-HPV. Teeth brushing before sleep was protective for beta/gamma-HPVs. Discussion The epidemiologic factors associated with oral infection with alpha-HPVs are different from those of beta/gamma-HPVs, suggesting different modes of acquisition and persistence.

Aim The mortality risk attributable to the classifications of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated the associations of mortality with COPD classifications and reduced lung function in a large longitudinal cohort in Taiwan. Methods A total of 388,401 adults (≥25 years of age) were recruited between 1996 and 2016 underwent 834,491 medical examinations including spirometry. We used the Global Initiative for Chronic Obstructive Lung Disease (GOLD) to establish the COPD classifications. A time-dependent Cox regression model was used to investigate the associations between the morality risk and COPD classifications. We also examined the associations between mortality and lung function. Results The mean age of the participants was 42.1 years, and the median follow-up duration was 16.2 years. We identified 28,283 natural-cause deaths, and the mortality rate was 4.7 per 1,000 person-years. The hazard ratios (HRs) [95%confidence interval (95%CI)] of mortality in the participants with restrictive spirometry pattern and COPD GOLD Ⅰ–Ⅳ were 1.31 (1.27–1.35), 1.18 (1.00–1.39), 1.43 (1.35–1.51), 1.78 (1.66–1.90), and 2.13 (1.94–2.34), respectively, with reference to the participants with normal lung function. The natural-cause mortality risk increased by 33% [HR(95%CI): 1.33 (1.28–1.39)] for participants with COPD. Reduced lung function was also associated with a higher mortality risk. Conclusions A more advanced classification of COPD was associated with a greater increase in the mortality risk. Our study suggests that early detection of COPD and slowing the disease progress in patients with COPD are crucial for mortality prevention.

Background and aim We validated a modified risk algorithm based on the Asia-Pacific Colorectal Screening (APCS) score that included body mass index (BMI) for prediction of advanced neoplasia. Methods Among 5744 Chinese asymptomatic screening participants undergoing a colonoscopy in Hong Kong from 2008 to 2012, a random sample of 3829 participants acted as the derivation cohort. The odds ratios for significant risk factors identified by binary logistic regression analysis were used to build a scoring system ranging from 0 to 6, divided into "average risk" (AR): 0; "moderate risk" (MR): 1-2; and "high risk" (HR): 3-6. The other 1915 subjects formed a validation cohort, and the performance of the score was assessed. Results The prevalence of advanced neoplasia in the derivation and validation cohorts was 5.4% and 6.0%, respectively (P = 0.395). Old age, male gender, family history of colorectal cancer, smoking, and BMI were significant predictors in multivariate regression analysis. A BMI cut-off at > 23 kg/m2 had better predictive capability and lower number needed to screen than that of > 25 kg/m2 . Utilizing the score developed, 8.4%, 57.4%, and 34.2% in the validation cohort were categorized as AR, MR, and HR, respectively. The corresponding prevalence of advanced neoplasia was 3.8%, 4.3%, and 9.3%. Subjects in the HR group had 2.48-fold increased prevalence of advanced neoplasia than the AR group. The c-statistics of the modified score had better discriminatory capability than that using predictors of APCS alone (c-statistics = 0.65 vs 0.60). Conclusions Incorporating BMI into the predictors of APCS score was found to improve risk prediction of advanced neoplasia and reduce colonoscopy resources.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited myocardial disease characterized by fibro‐fatty replacement of the right ventricular myocardium, and associated with paroxysmal ventricular arrhythmias and sudden cardiac death (SCD). It is currently the second most common cause of SCD after hypertrophic cardiomyopathy in young people

BACKGROUND AND AIM Colorectal cancer (CRC) incidence is rising among

Background It remains controversial whether weight change could influence the risks of colorectal cancer (CRC) and mortality. This study aimed to quantify the associations between full-spectrum changes in body mass index (BMI) and the risks of colorectal cancer (CRC) incidence, cancer-related and all-cause mortality among midlife to elder population. Methods A total of 81,388 participants who were free of cancer and aged 55 to 74 years from the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening program were involved. The percentage change of BMI was calculated as (BMI in 2006 - BMI at baseline)/BMI at baseline, and was categorized into nine groups: decrease (≥ 15.0%, 10.0–14.9%, 5.0–9.9%, 2.5–4.9%), stable (decrease/increase Results After 2006, there were 241 new CRC cases, 648 cancer-related deaths, and 2361 all-cause deaths identified. Overall, the associations between BMI change and CRC incidence and cancer-related mortality, respectively, were not statistically significant. Compared with participants whose BMI were stable, individuals who had a decrease in BMI were at increased risk of all-cause mortality, and the HRs were 1.21 (95% CI: 1.03–1.42), 1.65 (95% CI: 1.44–1.89), 1.84 (95% CI: 1.56–2.17), and 2.84 (95% CI: 2.42–3.35) for 2.5–4.9%, 5.0–9.9%, 10.0–14.9%, and ≥ 15.0% decrease in BMI, respectively. An L-shaped association between BMI change and all-cause mortality was observed. Every 5% decrease in BMI was associated with a 27% increase in the risk of all-cause mortality (HR = 1.27, 95% CI: 1.22–1.31, p Conclusions A decrease in BMI more than 5% shows a significantly increased risk of all-cause mortality among older individuals; but no significant association between increase in BMI and all-cause mortality. These findings emphasize the importance of body weight management in older population, and more studies are warranted to evaluate the cause-and-effect relationship between changes in BMI and cancer incidence/mortality.

Background Risk stratification in acute myocardial infarction (AMI) is important for guiding clinical management. Current risk scores are mostly derived from clinical trials with stringent patient selection. We aimed to establish and evaluate a composite scoring system to predict short-term mortality after index episodes of AMI, independent of electrocardiography (ECG) pattern, in a large real-world cohort. Methods Using electronic health records, patients admitted to our regional teaching hospital (derivation cohort, n=2127) and an independent tertiary care center (validation cohort, n=1276) with index acute myocardial infarction between January 2013 and December 2017 as confirmed by principal diagnosis and laboratory findings, were identified retrospectively. Results Univariate logistic regression was used as the primary model to identify potential contributors to mortality. Stepwise forward likelihood ratio logistic regression revealed that neutrophil-to-lymphocyte ratio, peripheral vascular disease, age, and serum creatinine (NPAC) were significant predictors for 90-day mortality (Hosmer-Lemeshow test, P=0.21). Each component of the NPAC score was weighted by beta-coefficients in multivariate analysis. The C-statistic of the NPAC score was 0.75, which was higher than the conventional Charlson's score (C-statistic=0.63). Application of a deep learning model to our dataset improved the accuracy of classification with a C-statistic of 0.81. Multivariate binary logistic regression Variable β Adjusted Odds ratio (95% CI) P-value Points Age ≥65 years 1.304 3.68 (2.63–5.17) NPAC deep learning model Conclusions The NPAC score comprised of four items from routine laboratory parameters and basic clinical information and can facilitate early identification of cases at risk of short-term mortality following index myocardial infarction. Deep learning model can serve as a gate-keeper to provide more accurate prediction to facilitate clinical decision making.

Background Patients with hypertension may develop thoracic aortic aneurysm (TAA) that can be asymptomatic but potentially life-threatening. We sought to assess the prevalence of asymptomatic TAA among hypertensive patients and define the effectiveness of a TAA point-of-care screening program using pocket-size mobile echocardiographic (PME) devices. Methods We prospectively performed transthoracic echocardiography for TAA screening using a PME device on 1529 hypertensive patients (age, 62y [30y to 85y], 824 men) who attended our hypertension specialist clinic between June 2016 and July 2018. Measurement of the dimensions of the aortic sinus, sinotubular junction, ascending aorta, aortic arch, and descending thoracic aorta were obtained through multiple standard echo views. Results The prevalence of TAA (defined as maximum aortic diameter of ≥4.5cm and/or >50% diameter of the adjacent aorta) in our study population was 7.3% (111/1529), with distal ascending aorta as the most frequent location (Figure). Multiple logistic regression analysis identified male gender, older age, and presence of heart valve disease as independent factors associated with TAA (all p Figure 1 Conclusions Asymptomatic TAA is common among asymptomatic hypertensive patients. Point-of-care use of PME device is effective in detecting TAA in a clinic setting. Such approach may be useful for early detection of TAA among at-risk patients allowing aggressive blood pressure control and early surgical intervention to prevent catastrophic complications such as aortic dissection or rupture. Acknowledgement/Funding Health and Medical Research Fund of the Hong Kong Government

Background Serrated lesions are precursors of approximately one-third of colorectal cancers (CRCs). They can be classified into hyperplastic polyps, sessile serrated polyps (SSPs), and traditional serrated adenomas (TSAs). Despite increasing knowledge on the histological categorisation of serrated lesions, the detection rate was highly variable and endoscopist dependent. This study aims to perform a systematic review and meta-analysis to determine the overall prevalence of serrated lesions and their subtypes in average-risk population undergoing CRC screening. Methods MEDLINE and Embase were searched to identify population-based studies that reported the prevalence of serrated lesions. Studies on average-risk populations using colonoscopy as a screening tool were included. The histologic classification of serrated lesions followed the criteria recommended by the World Health Organization. Metaprop was applied to model within-study variability by binomial distribution and Freeman-Tukey double arcsine transformation was adopted to stabilise the variances. The prevalence figures were presented by proportions and their 95% confidence intervals (CIs) using random-effects models. Results This meta-analysis included 17 studies involving 129,001 individuals. The overall prevalence rates of serrated lesions (19.0%, 95% CI=15.3%-23.0%), SSPs (2.5%, 95% CI=1.5%-3.8%) and TSAs (0.3%, 95% CI=0.1%-0.8%) were shown in figure 1 (figure 1). Subgroup analysis indicated their higher prevalence among male (22.0%, 95% CI=16.4%-28.2%) than female (14.0%, 95% CI=8.2%-21.0%), and Caucasian (25.9%, 95% CI=16.4%-28.2%) than Asian (14.6%, 95% CI=11.6%-18.2%). The prevalence of SSPs was also higher among Caucasian (2.9%, 95% CI=1.5%-4.7%) than Asian (0.7%, 95% CI=0.4%-1.2%). However, their prevalence were similar between male (2.9%, 95% CI=1.0%-5.7%) and female (2.4%, 95% CI=0.8%-4.9%). Conclusions This was the first systematic review and meta-analysis to determine the overall prevalence of serrated lesions and their different subtypes. The pooled prevalence estimates can be used as indicators for establishing high-quality CRC screening programmes. Future studies should be performed to evaluate the factors independently associated with the presence of serrated lesions, which could inform clinical practice to enhance their detection rate.

BackgroundFew studies have examined the associations between physical activity (PA), sedentary behaviour (SB) and risk of colorectal neoplasia (CN).MethodsWe systematically searched Medline, Embase, PsyInfo, Cochrane and other sources from their inception to 30 September 2018 for cohort, case-control and cross-sectional studies that evaluated these associations in asymptomatic, average-risk subjects. Random-effect models were used to estimate relative risks (RRs) of any-type CN, advanced CN, and non-advanced CN, respectively, in individuals with the highest versus the lowest level of PA and SB. Dose-response analyses and subgroup analyses were conducted. The I2 statistic was used to examine heterogeneity among studies.ResultsWe identified 32 observational studies, including 17 cross-sectional studies, 10 case-control studies and five longitudinal studies. PA (highest vs lowest) was inversely associated with risk for any-type CN (n=23 studies) and advanced CN (n=15 studies), with a RR of 0.77 (95% CI=0.71 to 0.83, I2=57.5%) and 0.73 (95% CI=0.63 to 0.82, I2=45.5%), respectively. There was no association between PA and non-advanced CN (n=5 studies). There was an as association between PA and any-type CN in both sexes, and also for the distal colon. We found no dose–response relationship between PA and any-type or advanced CN. Based on three studies identified, SB time (longest vs shortest) was associated with an increased risk of advanced CN (RR=1.24, 95% CI 1.04 to 1.49, I2=14.4%). No publication bias was detected by Begg’s test.ConclusionWe report a 23% lower relative risk of any type of CN and a 27% lower risk of advanced CN in people with the highest level of PA compared with those in the lowest.

Background and aims Risk stratification in acute myocardial infarction (AMI) is important for guiding clinical management. Current risk scores are mostly derived from clinical trials with stringent patient selection. We aimed to establish and evaluate a composite scoring system to improve short-term mortality classification after index episodes of AMI, independent of electrocardiography (ECG) pattern, in a large real-world cohort. Methods Using electronic health records, patients admitted to our regional teaching hospital (derivation cohort, n = 1747) and an independent tertiary care center (validation cohort, n = 1276), with index acute myocardial infarction between January 2013 and December 2017, as confirmed by principal diagnosis and laboratory findings, were identified retrospectively. Results Univariate logistic regression was used as the primary model to identify potential contributors to mortality. Stepwise forward likelihood ratio logistic regression revealed that neutrophil-to-lymphocyte ratio, peripheral vascular disease, age, and serum creatinine (NPAC) were significant for 90-day mortality (Hosmer- Lemeshow test, p = 0.21). Each component of the NPAC score was weighted by beta-coefficients in multivariate analysis. The C-statistic of the NPAC score was 0.75, which was higher than the conventional Charlson's score (C-statistic = 0.63). Judicious application of a deep learning model to our dataset improved the accuracy of classification with a C-statistic of 0.81. Conclusions The NPAC score comprises four items from routine laboratory parameters to basic clinical information and can facilitate early identification of cases at risk of short-term mortality following index myocardial infarction. Deep learning model can serve as a gatekeeper to facilitate clinical decision-making.

We tested the hypothesis that the risk of colorectal cancer (CRC), advanced colorectal neoplasia (ACN), and colorectal adenoma among screening participants with different first-degree relatives (FDRs) affected by CRC was similar.A multi-center, prospective colonoscopy study involving 16 Asia-Pacific regions was performed from 2008 to 2015. Consecutive self-referred CRC screening participants aged 40-70 years were recruited, and each subject received one direct optical colonoscopy. The prevalence of CRC, ACN, and colorectal adenoma was compared among subjects with different FDRs affected using Pearson's χAmong 11,797 asymptomatic subjects, the prevalence of CRC was 0.6% (none: 0.6%; siblings: 1.1%; mother: 0.5%; father: 1.2%; ≥2 members: 3.1%, P0.001), that of ACN was 6.5% (none: 6.1%; siblings: 8.3%; mother: 7.7%; father: 8.7%; ≥2 members: 9.3%, P0.001), and that of colorectal adenoma was 29.3% (none: 28.6%; siblings: 33.5%; mother: 31.8%; father: 31.1%; ≥2 members: 38.1%, P0.001). In multivariate regression analyses, subjects with at least one FDR affected were significantly more likely to have CRC (adjusted odds ratio (AOR)=2.02-7.89), ACN (AOR=1.55-2.06), and colorectal adenoma (AOR=1.31-1.92) than those without a family history. The risk of CRC (AOR=0.90, 95% confidence interval (CI) 0.34-2.35, P=0.830), ACN (AOR=1.07, 95% CI 0.75-1.52, P=0.714), and colorectal adenoma (AOR=0.96, 95% CI 0.78-1.19, P=0.718) in subjects with either parent affected was similar to that of subjects with their siblings affected.The risk of colorectal neoplasia was similar among subjects with different FDRs affected. These findings do not support the need to discriminate proband identity in screening participants with affected FDRs when their risks of colorectal neoplasia were estimated.

Objective There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. Design We measured relative abundance of Fusobacterium nucleatum ( Fn ), Peptostreptococcus anaerobius ( Pa ) and Parvimonas micra ( Pm ) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects. Results The abundance was higher for all three individual markers in patients with CRC than controls (p Fn in patients with advanced adenoma than controls (p=0.022). The marker Fn , when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p Conclusions This study identified marker Fn as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.

Waist-to-height ratio (WHtR) is superior to body mass index and waist circumference for measuring adult cardio-metabolic risk factors. However, there is no meta-analysis to evaluate its discriminatory power in children and adolescents. A meta-analysis was conducted using multiple databases, including Embase and Medline. Studies were included that utilized receiver-operating characteristics curve analysis and published area under the receiver-operating characteristics curves (AUC) for adiposity indicators with hyperglycaemia, elevated blood pressure, dyslipidemia, metabolic syndrome and other cardio-metabolic outcomes. Thirty-four studies met the inclusion criteria. AUC values were extracted and pooled using a random-effects model and were weighted using the inverse variance method. The mean AUC values for each index were greater than 0.6 for most outcomes including hypertension. The values were the highest when screening for metabolic syndrome (AUC > 0.8). WHtR did not have significantly better screening power than other two indexes in most outcomes, except for elevated triglycerides when compared with body mass index and high metabolic risk score when compared with waist circumference. Although not being superior in discriminatory power, WHtR is convenient in terms of measurement and interpretation, which is advantageous in practice and allows for the quick identification of children with cardio-metabolic risk factors at an early age.

SummaryBackground The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results. Aim To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC. Methods Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random-effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT). Results Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3–79.4%), 93.6% (95% CI 90.7–95.7%), 11.1 (95% CI 7.8–15.8) and 0.3 (95% CI 0.2–0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9–87.0%), 93.6% (95% CI 90.7–95.7%), 12.6 (95% CI 8.8–18.1) and 0.2 (95% CI 0.1–0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC. Conclusion Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.

Background: Information on the association between long-term exposure to PM2.5 and gastrointestinal cancer mortality is scarce. Objectives: This study investigated the association between long-term exposure to PM2.5 and deaths from gastrointestinal cancer and its subtypes in adults in Taiwan. Methods: A total of 385,650 Taiwanese adults (≥18 years old) jointed a standard medical examination program between 2001 and 2014 and were followed up until 2016. Their vital data were obtained from the National Death Registry maintained by the Ministry of Health and Welfare in Taiwan. We estimated the ambient PM2.5 concentration at individual’s address utilising a satellite-based spatiotemporal model at a resolution of 1 km2. Cox proportional hazard regression model was used to investigate the associations between ambient PM2.5 and deaths from gastrointestinal, stomach, colorectal and liver cancers. Results: We found that each 10 µg/m3 increase in PM2.5 was associated with an increased hazard risk (HR) of 1.09 (95% confidence interval (CI): 1.03–1.16) and 1.13 (95%CI: 1.02–1.24) in deaths from gastrointestinal and liver cancers, respectively. The association between PM2.5 and death from colorectal cancer was marginally statistically significant [HR: 1.13 (95%CI: 1.00–1.26)]. We did not find significant associations between PM2.5 and mortality from stomach cancer. Conclusions: Long-term exposure to ambient PM2.5 was associated with an increased risk of deaths from gastrointestinal cancers, liver cancer and also potentially colorectal cancer. Air pollution control strategies are necessary to reduce the burden of gastrointestinal cancer. Keywords: Long-term exposure, PM2.5 air pollution, Gastrointestinal cancer mortality, Live cancer mortality, Taiwan

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.

Background A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. Objectives To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. Study design Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. Results The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 μL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. Conclusions HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.

BackgroundCarbohydrate antigen-125 (CA125) is an ovarian cancer marker, but recent work has examined its role in risk stratification in heart failure. A recent meta-analysis examined its prognostic value in heart failure generally. However, there has been no systematic evaluation of its role specifically in acute heart failure (AHF).MethodsPubMed and EMBASE databases were searched until 11 May 2018 for studies that evaluated the prognostic value of CA125 in AHF.ResultsA total of 129 and 179 entries were retrieved from PubMed and EMBASE. Sixteen studies (15 cohort studies, 1 randomised trial) including 8401 subjects with AHF (mean age 71 years old, 52% male, mean follow-up 13 months, range of patients 525.1±598.2) were included. High CA125 levels were associated with a 68% increase in all-cause mortality (8 studies, HRs: 1.68, 95% CI 1.36 to 2.07; p2: 74%) and 77% increase in heart failure-related readmissions (5 studies, HRs: 1.77, 95% CI 1.22 to 2.59; p2: 73%). CA125 levels were higher in patients with fluid overload symptoms and signs compared with those without them, with a mean difference of 54.8 U/mL (5 studies, SE: 13.2 U/mL; p2: 78%).ConclusionOur meta-analysis found that high CA125 levels are associated with AHF symptoms, heart failure-related hospital readmissions and all-cause mortality. Therefore, CA125 emerges as a useful risk stratification tool for identifying high-risk patients with more severe fluid overload, as well as for monitoring following an AHF episode.