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Background The long-term effects of H. pylori eradication in preventing upper GI bleeding (UGIB) remains unknown. Aim To determine the long-term risks of UGIB after H. pylori eradication METHODS: We included all patients who had received clarithromycin-containing triple therapy for the treatment of H. pyliori infection between 2003 and 2012, without subsequent need for re-treatment. We included a propensity score (PS)-matched endoscopy cohort of H. pylori-negative patients as controls. The primary endpoint was the risk of subsequent UGIB. A multivariable Cox model was used to compute the hazard ratio (HR) of UGIB. Results We included 62 738 H. pylori-eradicated and 62 738 PS-matched H. pylori-negative patients, with a median follow-up of 8.1 years (IQR 5.5-10.6). The incidence of UGIB was 20.8 (95% CI 19.5-22.1) and 13.6 (95% CI 12.7-14.7) per 10 000 person-years in H. pylori-eradicated and H. pylori-negative patients, respectively. Compared to controls, H. pylori-eradicated patients had a significantly higher risk of UGIB (HR: 1.65, 95% CI 1.49-1.83). The risk of UGIB in H. pylori-eradicated patients increased after the first 2 years of follow up (HR: 2.18, 95% CI 1.91-2.49). Age-stratified analysis showed that patients >45 years had higher UGIB risk, even after eradication. Conclusions Despite H. pylori eradication, the long-term risk of UGIB was still higher than in H. pylori-negative control subjects. The protective effects of eradication therapy in preventing UGIB appeared to be limited to younger patients, and to within the first 2 years after eradication.

BACKGROUND: Previous studies have demonstrated the seasonal variations of non-variceal upper gastrointestinal bleeding (UGIB), but there is scanty data on lower gastrointestinal bleeding (LGIB) and the association with other meteorological parameters.METHODS: We included all patients hospitalized for UGIB and LGIB between 2009 and 2018 in Hong Kong. The monthly age-standardized and sex-standardized GIB incidences were fitted to meteorological data including average temperature (AT), maximum temperature (MaxT), minimum temperature (MinT), temperature range (TR), average precipitation, average atmospheric pressure (AtomP), and average relative humidity after adjusting for prescriptions of aspirin, proton pump inhibitors, and Helicobacter pylori eradication therapy using the autoregressive integrated moving average model.RESULTS: Despite a gradual decline in UGIB incidences, the incidences of UGIB were still higher in winter months. The incidence and fluctuation of both UGIB and LGIB were higher in the older age groups, especially those ≥80 years. The seasonality was only identified in those ≥60 years for UGIB, and only in those ≥80 years for LGIB. UGIB incidence was inversely associated with AT, MaxT, and MinT, but positively associated with TR and AtomP. LGIB was also significantly associated with AT, MaxT, MinT, and AtomP.CONCLUSION: Despite the changes in GIB incidences, the seasonal patterns of GIB were still marked in the elderly. With the aging population, the impacts of seasonal variations on GIB incidences could be considerable.

Although antithrombotic agents could increase the risk of postpolypectomy bleeding, interruption of these agents also increases the risk of thromboembolism (TE). We assessed the risks of postcolonoscopy TE events and their association with the interruption of antithrombotic agents.This was a retrospective cohort study including consecutive patients undergoing colonoscopy between January 2016 and March 2021. We determined the rates of postcolonoscopy TE events in patients taking various antithrombotic agents (with or without interruption), and in different patient groups according to indications for colonoscopy, underlying TE, and bleeding risks.Of the 6220 patients, 1755 (28.2%) were on antithrombotics. Overall, 20 patients (0.32%) developed TE events, and 25 (0.80%) of 3134 patients with polypectomy experienced major episodes of bleeding. Among all patients on antithrombotic agents, the highest rates of TE events were observed in patients on dual-antiplatelet therapy (4.65%; adjusted odds ratio [aOR], 28.0; 95% CI, 3.77-142.1) and clopidogrel (2.78%; aOR, 12.2; 95% CI, 2.10-57.0), compared with 0.11% among those not on antithrombotics. In patients interrupting anti-thrombotic agents, the risk of TE was increased compared to those on no agent as follows: stopping 2 or more antithrombotic agents (4.55%; aOR, 22.5; 95% CI, 1.09-158.0), monotherapy with clopidogrel (3.06%; aOR, 15.5; 95% CI, 2.86-69.6), warfarin (1.33%; aOR, 6.96; 95% CI, 1.14-33.5), or direct-acting oral anticoagulants (0.87%; aOR, 6.23; 95% CI, 1.22-26.8). Having an underlying high TE risk (aOR, 16.8; 95% CI, 6.33-46.6) was associated with higher postcolonoscopy TE events.The risk of post-colonoscopy thromboembolic events is low. However, the temporary interruption of antithrombotic agents, particularly stopping 2 or more agents, clopidogrel, warfarin, or direct-acting oral anticoagulants was associated with higher postcolonoscopy TE events, particularly in high-risk patients.

Background With the increasing use of medications that alter the risk of gastrointestinal bleeding (GIB), comprising aspirin, proton pump inhibitors (PPIs), and Helicobacter pylori eradication therapies, the trends of GIB are evolving. Objective The aim of this study is to determine and predict the trends of GIB and to evaluate the effects of population prescriptions of these medications on GIB incidences. Methods We retrieved patients hospitalized for GIB in all public hospitals in Hong Kong between 2009 and 2019. Monthly age- and sex-standardized GIB data were fitted and predicted, based on population prescriptions of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, other antiplatelet drugs, PPIs, and H. pylori therapies, using autoregressive integrated moving average model for time series analysis. Results The incidence of upper GIB (UGIB) showed a clear declining trend while lower GIB (LGIB) decreased slightly. Older population (>80 years) had the greatest decline in UGIB but was associated with an increase in LGIB. Prescriptions of PPIs and aspirin increased significantly with time. PPIs prescriptions were negatively associated with UGIB incidence (coefficient log(PPIs) -4.58; 95% confidence interval [CI]: -5.69, -3.47). H. pylori eradication in the previous month showed a nonsignificant trend on UGIB (coefficient -0.14; 95% CI: -0.30, 0.02). In contrast, aspirin increased the incidences of UGIB (coefficient 0.06; 95% CI: 0.04, 0.07) and LGIB (coefficient 0.04; 95% CI: 0.03, 0.05). NSAIDs, anticoagulants, and other antiplatelet drugs were not significantly associated with the trend of either UGIB or LGIB. UGIB is predicted to decline continuously but LGIB is projected to rise, particularly with increasing use of aspirin. Conclusions UGIB incidences were decreasing and had been surpassed by LGIB. Based on population prescriptions of aspirin and PPIs, divergent trends of upper and lower GIB are expected, especially in elderly.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

With the increasing use of nonsteroidal anti-inflammatory drugs (NSAIDs), the incidence of lower gastrointestinal (GI) complications is expected to increase. However, unlike up per GI complications, the burden, pathogenesis, prevention and treatment of NSAID-associated lower GI complications remain unclear. To date, no cost-effective and safe protec tive agent has been developed that can completely prevent or treat NSAID-related lower GI injuries. Selective COX-2 in hibitors, misoprostol, intestinal microbiota modulation, and some mucoprotective agents have been reported to show protective effects on NSAID-induced lower GI injuries. This re view aims to provide an overview of the current evidence on the prevention of NSAID-related lower GI injuries. (Gut Liver 2020;14:179-189)

Failure rates of clarithromycin-containing triple therapy for H. pylori are rising. To determine the trend of failure rates of clarithromycin-containing triple therapy in different age groups in Hong Kong over the past 15 years.This is a population-based retrospective age-period-cohort study involving all adult H. pylori-infected patients who had received the first course of clarithromycin-containing triple therapy in 2003-2017. Failed eradication was identified by the need of retreatment within 2 years of eradication. Logistic regression model was used to characterize the risk of retreatment.113,526 H. pylori-infected patients were included. The overall failure rate increased from 4.83% in 2003 to 10.2% in 2016 (p for linear trend0.001). When stratified by age of eradication, patients 75 years or above had the lowest retreatment rate of 5.11%, which progressively increased in younger patients (60-74 years: OR 1.26, 95% CI 1.15-1.38; 45-59 years: OR 1.36, 95% CI 1.24-1.48; 18-44 years: OR 1.55, 95% CI 1.41-1.69). The results remained consistent when stratified by year of birth, and period of eradication. Other risk factors for retreatment included female (OR 1.24, 95% CI 1.18-1.30), triple therapy containing metronidazole (OR 2.30, 95% CI 2.12-2.50), and shorter duration of therapy (10 days: OR 0.88, 95% CI 0.79-0.97; 14 days: OR 0.67, 95% CI 0.58-0.77 vs 7 days).While failure rates of clarithromycin-containing triple therapy progressively increased over the past 15 years, the failure rate was particularly high among younger patients, which could undermine the potential benefits of early H. pylori eradication.

Background: There is evidence supporting the association between Helicobacter pylori infection and colorectal cancer (CRC), but whether H. pylori eradication reduces the risk of CRC is still unknown. Objectives: To compare the incidence of CRC in subjects who had received H. pylori eradication therapy with general population. Design: A population-based retrospective cohort study. Methods: This study included all H. pylori-infected subjects who had received their first course of clarithromycin-containing triple therapy in 2003–2015 in Hong Kong. We compared the observed incidences of CRC in this H. pylori eradicated cohort with the expected incidences in the age- and sex-matched general population. The standardized incidence ratio (SIR) with 95% confidence interval (CI) was computed. Results: Among 96,572 H. pylori-eradicated subjects with a median follow-up of 9.7 years, 1417 (1.5%) developed CRC. Primary analysis showed no significant difference in the observed and expected incidences of CRC (SIR: 1.03, 95% CI: 0.97–1.09). However, when stratified according to the follow-up period, higher incidence of CRC was only observed in the first 5 years after eradication (SIR: 1.47, 95% CI: 1.39–1.55), but it was lower (SIR: 0.85, 95% CI: 0.74–0.99) than general population after 11 years. When stratified by tumor location, the observed incidence was higher for colon (SIR: 1.20, 95% CI: 1.12–1.29) but lower for rectal cancer (SIR: 0.90, 95% CI: 0.81–0.999) among H. pylori-eradicated subjects. Conclusions: H. pylori-infected subjects appeared to have a higher incidence of CRC initially, which declined progressively to a level lower than general population 10 years after H. pylori eradication, particularly for rectal cancer.

Interval colorectal cancers (CRCs), cancers diagnosed after a screening/surveillance examination in which no cancer is detected, and before the date of next recommended examination, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutational characteristics of interval CRCs in comparison with screen detected CRCs.We included 1175 CRCs documented in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and 3661 CRCs in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Multivariable Cox models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of death risk. Whole exome sequencing was conducted in 147 PLCO cases and 796 NHS/HPFS cases.A total of 619 deaths (312 CRC-specific) and 2404 deaths (1904 CRC-specific) were confirmed during follow-up of PLCO and NHS/HPFS, respectively. Compared with screen detected CRCs, interval CRCs had a multivariate-adjusted HR (95% CI) of 1.47 (1.21-1.78) for CRC-specific mortality and 1.27 (1.09-1.47) for overall mortality (meta-analysis combining all 3 cohorts). However, we did not observe significant differences in mutational features between interval and screen detected CRCs (false discovery rate adjusted P.05).Interval CRCs had a significantly increased risk of death compared with screen detected CRCs that were not explained by established clinical prognostic factors, including stage at diagnosis. The survival disadvantage of interval CRCs did not appear to be explained by differences in the genomic landscape of tumors characterized by whole exome sequencing.

Background:The variation in the pathogen type as well as the spatial heterogeneity of predictors make the generality of any associations with pathogen discovery debatable. Our previous work confirmed that the association of a group of predictors differed across different types of RNA viruses, yet there have been no previous comparisons of the specific predictors for RNA virus discovery in different regions. The aim of the current study was to close the gap by investigating whether predictors of discovery rates within three regions—the United States, China, and Africa—differ from one another and from those at the global level.Methods:Based on a comprehensive list of human-infective RNA viruses, we collated published data on first discovery of each species in each region. We used a Poisson boosted regression tree (BRT) model to examine the relationship between virus discovery and 33 predictors representing climate, socio-economics, land use, and biodiversity across each region separately. The discovery probability in three regions in 2010–2019 was mapped using the fitted models and historical predictors.Results:The numbers of human-infective virus species discovered in the United States, China, and Africa up to 2019 were 95, 80, and 107 respectively, with China lagging behind the other two regions. In each region, discoveries were clustered in hotspots. BRT modelling suggested that in all three regions RNA virus discovery was better predicted by land use and socio-economic variables than climatic variables and biodiversity, although the relative importance of these predictors varied by region. Map of virus discovery probability in 2010–2019 indicated several new hotspots outside historical high-risk areas. Most new virus species since 2010 in each region (6/6 in the United States, 19/19 in China, 12/19 in Africa) were discovered in high-risk areas as predicted by our model.Conclusions:The drivers of spatiotemporal variation in virus discovery rates vary in different regions of the world. Within regions virus discovery is driven mainly by land-use and socio-economic variables; climate and biodiversity variables are consistently less important predictors than at a global scale. Potential new discovery hotspots in 2010–2019 are identified. Results from the study could guide active surveillance for new human-infective viruses in local high-risk areas.Funding:FFZ is funded by the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk/). MEJW has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 874735 (VEO) (https://www.veo-europe.eu/).

Given the continued burden of COVID-19 worldwide, there is a high unmet need for data on the effect of social distancing and face mask use to mitigate the risk of COVID-19. We examined the association of community-level social distancing measures and individual face mask use with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported ‘always’ use of face mask was associated with a 62% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. Despite mass vaccination campaigns in many parts of the world, continued efforts at social distancing and face mask use remain critically important in reducing the spread of COVID-19.

BACKGROUND: Ticagrelor and prasugrel are third‐generation oral P2Y12 receptor antagonists with rapid onset and pronounced platelet inhibition. However, higher overall bleeding rates have been reported for these agents when compared with clopidogrel. // AIM: To compare the risk of gastrointestinal bleeding (GIB) among users of third‐generation P2Y12 inhibitors with clopidogrel. // METHODS: We systematically searched for published randomised controlled trials of ticagrelor or prasugrel versus clopidogrel until September 2018. The primary outcome was the risk of GIB among users of third‐generation P2Y12 inhibitors when compared to clopidogrel, expressed as risk ratio (RR) and 95% confidence interval (CI). The rates of non‐coronary artery bypass graft (CABG) major bleeding, life‐threatening bleeding, fatal bleeding, and intracranial bleeding were analysed as secondary outcomes. // RESULTS: Forty‐one studies were included in the analysis of non‐CABG major bleeding, of which 12 were included in the analysis of GIB including 58 678 patients. Third‐generation P2Y12 inhibitors were associated with higher risk of GIB as compared with clopidogrel (RR 1.28, 95% CI 1.13‐1.46). The findings were consistent for upper (RR 1.32, 95% CI 1.05‐1.67) and unspecified GIB (RR 1.25, 95% CI 1.01‐1.53), but not lower GIB (RR 1.25, 95% CI 0.95‐1.65). Subgroup analysis showed higher GIB risk in prasugrel studies (RR 1.40, 95% CI 1.10‐1.77) than in ticagrelor studies (RR 1.15, 95% CI 0.94‐1.39). Third‐generation P2Y12 inhibitors also increased the risk of non‐CABG major bleeding (RR 1.18, 95% CI 1.08‐1.28). // CONCLUSION: Third‐generation P2Y12 inhibitors were associated with increased risk of GIB and non‐CABG major bleeding when compared with clopidogrel.

Countries of the World Health Organization (WHO) African Region have experienced a wide range of coronavirus disease 2019 (COVID-19) epidemics. This study aimed to identify predictors of the timing of the first COVID-19 case and the per capita mortality in WHO African Region countries during the first and second pandemic waves and to test for associations with the preparedness of health systems and government pandemic responses. Using a region-wide, country-based observational study, we found that the first case was detected earlier in countries with more urban populations, higher international connectivity and greater COVID-19 test capacity but later in island nations. Predictors of a high first wave per capita mortality rate included a more urban population, higher pre-pandemic international connectivity and a higher prevalence of HIV. Countries rated as better prepared and having more resilient health systems were worst affected by the disease, the imposition of restrictions or both, making any benefit of more stringent countermeasures difficult to detect. Predictors for the second wave were similar to the first. Second wave per capita mortality could be predicted from that of the first wave. The COVID-19 pandemic highlights unanticipated vulnerabilities to infectious disease in Africa that should be taken into account in future pandemic preparedness planning., A new study from the WHO African Region identifies features of countries that predict timing of the first case and the per capita mortality rate for the first and second waves of the COVID-19 epidemics.

Early reports raised concern that use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19). Users of the COVID Symptom Study smartphone application reported use of aspirin and other NSAIDs between March 24 and May 8, 2020. Users were queried daily about symptoms, COVID-19 testing, and healthcare seeking behavior. Cox proportional hazards regression was used to determine the risk of COVID-19 among according to aspirin or non-aspirin NSAID users. Among 2,736,091 individuals in the U.S., U.K., and Sweden, we documented 8,966 incident reports of a positive COVID-19 test over 60,817,043 person-days of follow-up. Compared to non-users and after stratifying by age, sex, country, day of study entry, and race/ethnicity, non-aspirin NSAID use was associated with a modest risk for testing COVID-19 positive (HR 1.23 [1.09, 1.32]), but no significant association was observed among aspirin users (HR 1.13 [0.92, 1.38]). After adjustment for lifestyle factors, comorbidities and baseline symptoms, any NSAID use was not associated with risk (HR 1.02 [0.94, 1.10]). Results were similar for those seeking healthcare for COVID-19 and were not substantially different according to lifestyle and sociodemographic factors or after accounting for propensity to receive testing. Our results do not support an association of NSAID use, including aspirin, with COVID-19 infection. Previous reports of a potential association may be due to higher rates of comorbidities or use of NSAIDs to treat symptoms associated with COVID-19.One Sentence SummaryNSAID use is not associated with COVID-19 risk.

Background There is limited prior investigation of the combined influence of personal and community-level socioeconomic factors on racial/ethnic disparities in individual risk of coronavirus disease 2019 (COVID-19). Methods We performed a cross-sectional analysis nested within a prospective cohort of 2,102,364 participants from March 29, 2020 in the United States (US) and March 24, 2020 in the United Kingdom (UK) through December 02, 2020 via the COVID Symptom Study smartphone application. We examined the contribution of community-level deprivation using the Neighborhood Deprivation Index (NDI) and the Index of Multiple Deprivation (IMD) to observe racial/ethnic disparities in COVID-19 incidence. ClinicalTrials.gov registration: NCT04331509. Findings Compared with non-Hispanic White participants, the risk for a positive COVID-19 test was increased in the US for non-Hispanic Black (multivariable-adjusted odds ratio [OR], 1.32; 95% confidence interval [CI], 1.18–1.47) and Hispanic participants (OR, 1.42; 95% CI, 1.33–1.52) and in the UK for Black (OR, 1.17; 95% CI, 1.02–1.34), South Asian (OR, 1.39; 95% CI, 1.30–1.49), and Middle Eastern participants (OR, 1.38; 95% CI, 1.18–1.61). This elevated risk was associated with living in more deprived communities according to the NDI/IMD. After accounting for downstream mediators of COVID-19 risk, community-level deprivation still mediated 16.6% and 7.7% of the excess risk in Black compared to White participants in the US and the UK, respectively. Interpretation Our results illustrate the critical role of social determinants of health in the disproportionate COVID-19 risk experienced by racial and ethnic minorities. Funding Please refer to the Funding section at the end of the article.

Importance Although aspirin is recommended for the prevention of colorectal cancer (CRC) among adults aged 50 to 59 years, recent data from a randomized clinical trial suggest a lack of benefit and even possible harm among older adults. Objective To examine the association between aspirin use and the risk of incident CRC among older adults. Design, setting, and participants A pooled analysis was conducted of 2 large US cohort studies, the Nurses' Health Study (June 1, 1980-June 30, 2014) and Health Professionals Follow-up Study (January 1, 1986-January 31, 2014). A total of 94 540 participants aged 70 years or older were included and followed up to June 30, 2014, for women or January 31, 2014, for men. Participants with a diagnosis of any cancer, except nonmelanoma skin cancer, or inflammatory bowel disease were excluded. Statistical analyses were conducted from December 2019 to October 2020. Main outcomes and measures Cox proportional hazards models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for incident CRC. Results Among the 94 540 participants (mean [SD] age, 76.4 [4.9] years for women, 77.7 [5.6] years for men; 67 223 women [71.1%]; 65 259 White women [97.1%], 24 915 White men [96.0%]) aged 70 years or older, 1431 incident cases of CRC were documented over 996 463 person-years of follow-up. After adjustment for other risk factors, regular use of aspirin was associated with a significantly lower risk of CRC at or after age 70 years compared with nonregular use (HR, 0.80; 95% CI, 0.72-0.90). However, the inverse association was evident only among aspirin users who initiated aspirin use before age 70 years (HR, 0.80; 95% CI, 0.67-0.95). In contrast, initiating aspirin use at or after 70 years was not significantly associated with a lower risk of CRC (HR, 0.92; 95% CI, 0.76-1.11). Conclusions and relevance Initiating aspirin at an older age was not associated with a lower risk of CRC in this pooled analysis of 2 cohort studies. In contrast, those who used aspirin before age 70 years and continued into their 70s or later had a reduced risk of CRC.

Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.

Longitudinal clustering of symptoms can predict the need for respiratory support in severe COVID-19., As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presentations. Clustering was validated on an independent replication dataset between 1 and 28 May 2020. Using the first 5 days of symptom logging, the ROC-AUC (receiver operating characteristic – area under the curve) of need for respiratory support was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.

Background: WHO African Region countries have experienced very different COVID-19 epidemics. This study aimed to identify predictors for the timing of the first COVID-19 case and the per capita mortality rate during the first and second pandemic wave in the region, and to test for any impact of countermeasures. Methods: We performed a region-wide, country-based observational study. Data on COVID-19 cases and deaths for all 47 countries in the WHO African Region were obtained from the WHO COVID-19 Dashboard. A set of predictors classified to nine categories were collected and used as explanatory variables. We applied Cox proportional hazards regression models, generalized linear mixed models and multinomial logistic regression models as appropriate. Findings: Predictors for an earlier first case were a more urban population, high volume of international air travel and more land borders, and better COVID-19 test capacity. Predictors for a high per capita mortality rate during the first wave were a more urban population, more pre-pandemic international air travel and higher prevalence of HIV. The stringency and timing of government restrictions on behaviour were not associated with a lower per capita mortality rate in the first wave. A more urban population and a higher infectious disease resilience score were associated with more stringent restrictions and/or a higher per capita mortality rate in the first wave. The predictor set for the second wave was similar, and first wave per capita mortality predicted that in the second wave. These results were not altered when measures of national testing effort were included in the models. Interpretation: COVID-19 in Africa arrived earlier and caused greater mortality in countries with more international travel and a more urban population. Mortality was exacerbated by high HIV prevalence; it is not clear whether this is a direct or indirect effect. Countries that were better prepared and judged to have more resilient health systems were worst affected, both by the disease and by the imposition of restrictions. The COVID-19 pandemic highlights unanticipated vulnerabilities to infectious disease in Africa. Funding Statement: National Institute for Health Research, Darwin Trust of Edinburgh Declaration of Interests: The authors disclose no conflicts of interest.

Given the continued burden of COVID-19 worldwide, there is a high unmet need for data on the effect of social distancing and face mask use to mitigate the risk of COVID-19. We examined the association of community-level social distancing measures and individual face mask use with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported ‘always’ use of face mask was associated with a 62% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. Despite mass vaccination campaigns in many parts of the world, continued efforts at social distancing and face mask use remain critically important in reducing the spread of COVID-19., Estimating the effectiveness of COVID-19 control measures requires large prospective data including symptoms and personal risk factors. Here, the authors used data from smartphone-based application and found that individual face mask use was associated with a 64% reduced risk of COVID-19 symptoms.

ObjectivesFurazolidone containing regimen is effectivefor Helicobacter pylori (H. pylori) infection, but its safetyremains controversial. To assess the safety of furazolidone containing regimenin H. pylori infection.DesignA systematic review and meta-analysis.Data sourcesPubMed, Embase, Cochrane Library, Web of Science and Scopus databases were systematically searched for eligible randomised controlled trials.Eligibility criteriaStudies comparing furazolidone with non-furazolidone-containing regimen, variable durations or doses of furazolidone were included.Data extraction and synthesisTwo reviewers independently selected studies and extracted data. Primary outcomes were the risk of total adverse events (AEs), serious AEs and severe AEs, expressed as relative risk (RR) with 95% CI. Secondary outcomes contained the incidence of individual adverse symptoms, AE-related treatment discontinuation and compliance.ResultsTwenty-six articles were identified from 2039 searched records, of which 14 studies (n=2540) compared furazolidone with other antibiotics. The eradication rates of furazolidone-containing regimen were higher than those of other antibiotics in both intention-to-treat (RR 1.06, 95% CI 1.01 to 1.12) and per-protocol analysis (RR 1.05, 95% CI 1.00 to 1.10). Only two serious AEs were reported in furazolidone group (2/1221, 0.16%). No significant increased risk was observed for the incidence of total AEs (RR 1.04, 95% CI 0.89 to 1.21) and severe AEs (RR 1.81, 95% CI 0.91 to 3.60). Twelve studies (n=3139) compared different durations of furazolidone, and four studies (n=343) assessed variable doses. Elevated risk of total AEs and severe AEs were only found in a high daily dose of furazolidone rather than prolonged duration. The incidence of AE-related treatment discontinuation and compliance of patients were all similar, irrespective of dose and duration adjustments.ConclusionFurazolidone-containing regimen has a similar risk of AEs and compliance as non-furazolidone-containing regimen. A low daily dose of 200 mg is well-tolerated for 14 day regimen and should be first considered.PROSPERO registration numberCRD42019137247

BackgroundRacial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk.MethodsWe used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups.ResultsWe documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups.ConclusionsOur results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.

BackgroundData for frontline healthcare workers (HCWs) and risk of SARS-CoV-2 infection are limited and whether personal protective equipment (PPE) mitigates this risk is unknown. We evaluated risk for COVID-19 among frontline HCWs compared to the general community and the influence of PPE.MethodsWe performed a prospective cohort study of the general community, including frontline HCWs, who reported information through the COVID Symptom Study smartphone application beginning on March 24 (United Kingdom, U.K.) and March 29 (United States, U.S.) through April 23, 2020. We used Cox proportional hazards modeling to estimate multivariate-adjusted hazard ratios (aHRs) of a positive COVID-19 test.FindingsAmong 2,035,395 community individuals and 99,795 frontline HCWs, we documented 5,545 incident reports of a positive COVID-19 test over 34,435,272 person-days. Compared with the general community, frontline HCWs had an aHR of 11·6 (95% CI: 10·9 to 12·3) for reporting a positive test. The corresponding aHR was 3·40 (95% CI: 3·37 to 3·43) using an inverse probability weighted Cox model adjusting for the likelihood of receiving a test. A symptom-based classifier of predicted COVID-19 yielded similar risk estimates. Compared with HCWs reporting adequate PPE, the aHRs for reporting a positive test were 1·46 (95% CI: 1·21 to 1·76) for those reporting PPE reuse and 1·31 (95% CI: 1·10 to 1·56) for reporting inadequate PPE. Compared with HCWs reporting adequate PPE who did not care for COVID-19 patients, HCWs caring for patients with documented COVID-19 had aHRs for a positive test of 4·83 (95% CI: 3·99 to 5·85) if they had adequate PPE, 5·06 (95% CI: 3·90 to 6·57) for reused PPE, and 5·91 (95% CI: 4·53 to 7·71) for inadequate PPE.InterpretationFrontline HCWs had a significantly increased risk of COVID-19 infection, highest among HCWs who reused PPE or had inadequate access to PPE. However, adequate supplies of PPE did not completely mitigate high-risk exposures.FundingZoe Global Ltd., Wellcome Trust, EPSRC, NIHR, UK Research and Innovation, Alzheimer’s Society, NIH, NIOSH, Massachusetts Consortium on Pathogen ReadinessRESEARCH IN CONTEXTEvidence before this studyThe prolonged course of the coronavirus disease 2019 (COVID-19) pandemic, coupled with sustained challenges supplying adequate personal protective equipment (PPE) for frontline healthcare workers (HCW), have strained global healthcare systems in an unprecedented fashion. Despite growing awareness of this problem, there are few data to inform policy makers on the risk of COVID-19 among HCWs and the impact of PPE on their disease burden. Prior reports of HCW infections are based on cross sectional data with limited individual-level information on risk factors for infection. A PubMed search for articles published between January 1, 2020 and May 5, 2020 using the terms “covid-19”, “healthcare workers”, and “personal protective equipment,” yielded no population-scale investigations exploring this topic.Added value of this studyIn a prospective study of 2,135,190 individuals, frontline HCWs may have up to a 12-fold increased risk of reporting a positive COVID-19 test. Compared with those who reported adequate availability of PPE, frontline HCWs with inadequate PPE had a 31% increase in risk. However, adequate availability of PPE did not completely reduce risk among HCWs caring for COVID-19 patients.Implications of all the available evidenceBeyond ensuring adequate availability of PPE, additional efforts to protect HCWs from COVID-19 are needed, particularly as lockdown is lifted in many regions of the world.

We performed a meta-analysis of all published studies to determine the diagnostic accuracy of artificial intelligence (AI) on histology prediction and detection of colorectal polyps.We searched Embase, PubMed, Medline, Web of Science, and Cochrane library databases to identify studies using AI for colorectal polyp histology prediction and detection. The quality of included studies was measured by the Quality Assessment of Diagnostic Accuracy Studies tool. We used a bivariate meta-analysis following a random-effects model to summarize the data and plotted hierarchical summary receiver operating characteristic curves. The area under the hierarchical summary receiver operating characteristic curve (AUC) served as an indicator of the diagnostic accuracy and during head-to-head comparisons.A total of 7680 images of colorectal polyps from 18 studies were included in the analysis of histology prediction. The accuracy of the AI (AUC) was .96 (95% confidence interval [CI], .95-.98), with a corresponding pooled sensitivity of 92.3% (95% CI, 88.8%-94.9%) and specificity of 89.8% (95% CI, 85.3%-93.0%). The AUC of AI using narrow-band imaging (NBI) was significantly higher than the AUC using non-NBI (.98 vs .84, P .01). The performance of AI was superior to nonexpert endoscopists (.97 vs .90, P .01). For characterization of diminutive polyps using a deep learning model with nonmagnifying NBI, the pooled negative predictive value was 95.1% (95% CI, 87.7%-98.1%). For polyp detection, the pooled AUC was .90 (95% CI, .67-1.00) with a sensitivity of 95.0% (95% CI, 91.0%-97.0%) and a specificity of 88.0% (95% CI, 58.0%-99.0%).AI was accurate in histology prediction and detection of colorectal polyps, including diminutive polyps. The performance of AI was better under NBI and was superior to nonexpert endoscopists. Despite the difference in AI models and study designs, AI performances are rather consistent, which could serve as a reference for future AI studies.

BACKGROUND & AIMS: Little is known about risk of upper gastrointestinal bleeding (UGIB) in patients failed by Helicobacter pylori eradication therapy. We investigated the effects of different time until retreatment, after failure of initial H pylori eradication therapy, on subsequent risk of UGIB.METHODS: We performed a territory-wide retrospective cohort study of 70,518 patients with H pylori infection who had received their first course of clarithromycin-based triple therapy from January 2003 through December 2012 in Hong Kong. Patients who required retreatment after failed initial therapy (n= 8330, 11.8%) were categorized based on time between initial and final H pylori eradication (3 months or less, 3-12 months, and more than 12 months). We collected clinical data from 30 days after prescription of the last course of H pylori therapy until hospitalization for non-variceal UGIB, death, or the end of the study (30 Jun 2016; median follow-up time, 7.65 years). The primary outcome was difference in development UGIB (determined from ICD-9 codes) between patients who required retreatment and those who did not (reference group).RESULTS: Compared with the reference group, patients who required retreatment had an overall higher risk of UGIB, even after last eradication therapy (adjusted hazard ratio (HR), 1.50, 95% CI, 1.34-1.69). There was a progressive increase in risk of UGIB with longer time from initial until final eradication therapy: hazard ratio for time less than 3 months, 1.16; 95% CI, 0.88-1.54, hazard ratio for time 3-12 months, 1.35; 95% CI, 1.07-1.69, and hazard ratio for time more than 12 months, 1.68; 95% CI, 1.46-1.94 (P for trend = .038).CONCLUSION: In a retrospective study of patients in Hong Kong, we found that those failed by initial H pylori eradication have an increased risk of UGIB, compared to patients who responded to the initial therapy. Risk increased progressively with longer time until retreatment. Early retreatment within 3 months should be considered to minimize subsequent UGIB risk.

Supplemental material, sj-pdf-1-tag-10.1177_1756284820967275 for Risk of malignancies in patients with inflammatory bowel disease who used thiopurines as compared with other indications: a territory-wide study by Kelvin Y. C. Zheng, Chuan-Guo Guo, Irene O. L. Wong, Lijia Chen, Ho Yin Chung, Ka Shing Cheung and Wai K. Leung in Therapeutic Advances in Gastroenterology

OBJECTIVE We aimed to investigate the efficacy of a split-dose 4-L polyethylene glycol (PEG) regimen for the quality of bowel preparation in Asian patients with previous colorectal surgery for colorectal cancer (CRC). METHODS This was a prospective, single-center, randomized controlled, endoscopist-blinded study. Patients with previous colorectal surgery for CRC were randomly allocated to a routine, morning-only 2-L PEG (2-MO) group or a split-dose 4-L PEG (4-SD) group. The primary outcome was a successful bowel preparation rate. Secondary outcomes were polyp detection rate (PDR), adenoma detection rate (ADR), patient compliance, satisfaction, tolerance, willingness to repeat the preparation and difficulty of the bowel preparation process. RESULTS In total, 187 patients were included (93 in the 2-MO group, 94 in the 4-SD group) in this study. The rate of successful bowel preparation in the 4-SD group was higher than in the 2-MO group (89.4% vs 66.7%, P

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for depression but there is a concern about the risk of upper gastrointestinal bleeding (UGIB). Past studies, however, are largely confounded by the presence of Helicobacter pylori (HP).AIM: To evaluate the UGIB risk of SSRI users after treatment for HP.METHODS: This was a propensity score (PS) matched cohort study with patients who used SSRI after receiving HP eradication therapy from the Hong Kong territory-wide healthcare database. The primary outcome was hospitalisation for nonvariceal UGIB. PS matching analysis with a ratio of 1:2 plus Cox regression model was used to compute the hazards ratios (HR) and 95% CI of UGIB risk.RESULTS: In this study, 3358 SSRI users and 57 906 non-users were included. The median follow-up duration was 7.74 (interquartile range 5.32-10.42) years. The crude incidence of hospitalisation for UGIB was 3.98 (95% CI 3.80-4.16) per 1000 person-years. In the PS matching analysis of 3358 SSRI users with 6716 non-users, SSRI was associated with a higher risk of UGIB compared to non-users (HR 1.95, 95% CI 1.41-2.70). This result was consistent in sensitivity analysis with 1:1 PS matching (HR 2.13, 95% CI 1.50-3.02) and multivariable analysis with 1-month intervals (HR 1.81, 95% CI 1.34-2.45) or 3-month intervals (HR 1.61, 95% CI 1.20-2.17). After stratifying by age, the increased risk of SSRI was only significant among patients >50 years.CONCLUSION: SSRI users have a higher risk of hospitalisation for nonvariceal UGIB after treatment for HP, particularly among older patients.

ObjectiveThe risk of GI bleeding (GIB) in aspirin users after Helicobacter pylori (HP) eradication remains poorly defined. We characterised the incidences and temporal trends of hospitalisations for all GIB in aspirin users after HP eradication therapy.DesignBased on a territory-wide health database, we identified all patients who had received the first course of clarithromycin-based triple therapy between 2003 and 2012. Patients were divided into three cohorts according to aspirin use: new users (commenced after HP eradication), chronic users (commenced before and resumed after HP eradication) and non-users. The primary outcome was to determine the risk of hospitalisation for GIB.ResultsWe included 6985 new aspirin users, 5545 chronic users and 48 908 non-users. The age-adjusted and sex-adjusted incidence of hospitalisation for all GIB in new, chronic and non-users was 10.4, 7.2 and 4.6 per 1000 person-years, respectively. Upper and lower GIB accounted for 34.7% and 45.3% of all bleeding, respectively. Compared with chronic users, new users had a higher risk of GIB (HR with propensity score matching: 1.89; 95% CI 1.29 to 2.70). Landmark analysis showed that the increased risk in new aspirin users was only observed in the first 6 months for all GIB (HR 2.10, 95% CI 1.41 to 3.13) and upper GIB (HR 2.52, 95% CI 1.38 to 4.60), but not for lower GIB.ConclusionNew aspirin users had a higher risk of GIB than chronic aspirin users, particularly during the initial 6 months. Lower GIB is more frequent than upper GIB in aspirin users who had HP eradicated.