Air pollution and the risk of incident chronic kidney disease in patients with diabetes: An exposure-response analysis.

Impact of air pollution on incident chronic kidney disease (CKD) in diabetic patients is insufficiently studied. We aimed to examine exposure-response associations of PM2.5, PM10, PM2.5-10, NO2, and NOX with incident CKD in diabetic patients in the UK. We also widened exposure level of PM2.5 and examined PM2.5-CKD association in diabetic patients across the entire range of global concentration. Based on data from UK biobank cohort, we applied Cox proportional hazards models and the shape constrained health impact function to investigate the associations between air pollutants and incident CKD in diabetic patients. Global exposure mortality model was applied to combine the PM2.5-CKD association in diabetic patients in the UK with all other published associations. Multiple air pollutants were positively associated with incident CKD in diabetic patients in the UK, with hazard ratios (HRs) of 1.034 (95 %CI: 1.015-1.053) and 1.021 (95 %CI: 1.007-1.036) for every 1 µg/m3 increase in PM2.5 and PM10 concentration, and 1.113 (95 %CI: 1.053-1.177) and 1.058 (95 %CI: 1.027-1.091) for every 10 µg/m3 increase in NO2 and NOX concentration, respectively. For PM2.5-10, associations with CKD in diabetic patients did not reach the statistical significance. Exposure-response associations with CKD in diabetic patients showed a near-linear trend for PM2.5, PM10, NO2, and NOX in the UK, whereas PM2.5-DKD associations in the globe exhibited a non-linear increasing trend. This study supports that air pollution could significantly increase the risk of CKD onset in diabetic patients.

Blue-light imaging or narrow-band imaging for proximal colonic lesions: a prospective randomized tandem colonoscopy study.

BACKGROUND AND AIMS: Blue-light imaging (BLI) is a new image-enhanced endoscopy with a wavelength filter similar to narrow-band imaging (NBI). We compared the 2 with white-light imaging (WLI) on proximal colonic lesion detection and miss rates. METHODS: In this 3-arm prospective randomized study with tandem examination of the proximal colon, we enrolled patients aged ≥40 years. Eligible patients were randomized in 1:1:1 ratio to receive BLI, NBI, or WLI during the first withdrawal from the proximal colon. The second withdrawal was performed using WLI in all patients. Primary outcomes were proximal polyp (pPDRs) and adenoma (pADRs) detection rates. Secondary outcomes were miss rates of proximal lesions found on tandem examination. RESULTS: Of 901 patients included (mean age, 64.7 years; 52.9% men), 48.1% underwent colonoscopy for screening or surveillance. The corresponding pPDRs of the BLI, NBI, and WLI groups were 45.8%, 41.6, and 36.6%, whereas the corresponding pADRs were 36.6%, 33.8%, and 28.3%. There was a significant difference in pPDR and pADR between BLI and WLI groups (difference, 9.2% [95% confidence interval {CI}, 3.3-16.9] and 8.3% [95% CI, 2.7-15.9]) and between NBI and WLI groups (difference, 5.0% [95% CI, 1.4-12.9] and 5.6% [95% CI, 2.1-13.3]). Proximal adenoma miss rates were significantly lower with BLI (19.4%) than with WLI (27.4%; difference, -8.0%; 95% CI, -15.8 to -.1) but not between NBI (27.2%) and WLI. CONCLUSIONS: Both BLI and NBI were superior to WLI on detecting proximal colonic lesions, but only BLI had lower proximal adenoma miss rates than WLI. (Clinical trial registration number: NCT03696992.).

Long-term effect of Helicobacter pylori eradication on colorectal cancer incidences.

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.

Risk of hospitalization for upper gastrointestinal bleeding in Helicobacter pylori eradicated patients newly started on warfarin or direct oral anticoagulants: A population-based cohort study.

BACKGROUND: To investigate risks of hospitalization for upper gastrointestinal bleeding (UGIB) in H. pylori-eradicated patients newly started on warfarin or direct oral anti-coagulants (DOACs). METHODS: We identified all patients who had previously received H. pylori eradication therapy or were found to have no H. pylori on endoscopy and were then newly started on warfarin or DOACs from a population-based electronic healthcare database. Primary analysis was the risk of UGIB between warfarin and DOACs users in H. pylori-eradicated patients. Secondary analysis included the UGIB risk between H. pylori-eradicated and H. pylori-negative patients who were newly started on warfarin or DOACs. The hazard ratio (HR) of UGIB was approximated by pooled logistic regression model incorporating the inverse propensity of treatment weightings with time-varying covariables. RESULTS: Among H. pylori-eradicated patients, DOACs had a significantly lower risk of UGIB (HR: 0.26, 95% CI 0.09-0.71) compared with warfarin. In particular, lower UGIB risks with DOACs were observed among older (≥65 years) patients, female, those without a history of UGIB or peptic ulcer, or ischemic heart disease, and non-users of acid-suppressive agents or aspirin. Secondary analysis showed no significant difference in UGIB risk between H. pylori-eradicated and H. pylori-negative patients newly started on warfarin (HR: 0.63,95% CI 0.33-1.19) or DOACs (HR: 1.37, 95% CI 0.45-4.22). CONCLUSIONS: In H. pylori-eradicated patients, new users of DOACs had a significantly lower risk of UGIB than new warfarin users. Furthermore, the risk of UGIB in new warfarin or DOACs users was comparable between H. pylori-eradicated and H. pylori-negative patients.

Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study.

BACKGROUND& AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical and Genomic Characterization of Interval Colorectal Cancer in 3 Prospective Cohorts.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Predictors of human-infective RNA virus discovery in the United States, China, and Africa, an ecological study.

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/).

Age of eradication and failure rates of clarithromycin-containing triple therapy for Helicobacter pylori: A 15-year population-based study.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 trend <0.001). 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). CONCLUSIONS: 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.

Timing of prior exposure to antibiotics and failure of Helicobacter pylori eradication: a population-based study.

BACKGROUND: The success rate of conventional Helicobacter pylori eradication therapy is declining, due to rising antibiotic resistance. OBJECTIVES: To determine the temporal effects of prior antibiotic exposure on eradication outcome. PATIENTS AND METHODS: This is a retrospective cohort study including all H. pylori-infected patients who received their first course of clarithromycin-containing triple therapy in 2003-18. Prior antibiotic exposures before H. pylori eradication therapy (up to 180 days, 1 year or 3 years) were retrieved. A logistic regression model was used to evaluate the association between different timings of previous antibiotic exposure, recent (within 30/60 days) or distant period, and the need for retreatment for H. pylori. RESULTS: A total of 120 787 H. pylori-infected patients were included. Prior exposure to any antibiotics within 180 days was associated with a higher risk of retreatment (OR 1.18, 95% CI 1.13-1.24) and the risk progressively increased with longer duration of antibiotic use. The results were consistent for prior exposure up to 1 year (OR 1.26, 95% CI 1.20-1.31) or 3 years (OR 1.30, 95% CI 1.25-1.35). However, when compared with those without prior antibiotic exposure, recent exposure (within 30 days) did not increase the risk of retreatment, which was consistent for analysis with prior antibiotic exposure up to 3 years. Notably, recent use of cephalosporins within 30/60 days and nitroimidazole within 30 days had significantly lower risks of retreatment. CONCLUSIONS: Any prior antibiotic exposure increased the risk of treatment failure of clarithromycin-containing triple therapy. Recent exposures to some classes of antibiotics may paradoxically increase treatment success.

Long-term risk of upper gastrointestinal bleeding after Helicobacter pylori eradication: a population-based cohort study.

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.

Predictors of COVID-19 epidemics in countries of the World Health Organization African Region.

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.

Associations of seasonal variations and meteorological parameters with incidences of upper and lower gastrointestinal bleeding.

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.

Race, ethnicity, community-level socioeconomic factors, and risk of COVID-19 in the United States and the United Kingdom.

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.

Association of social distancing and face mask use with risk of COVID-19.

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.

Divergent trends of hospitalizations for upper and lower gastrointestinal bleeding based on population prescriptions of aspirin, proton pump inhibitors and Helicobacter pylori eradication therapy: Trends of upper and lower gastrointestinal bleeding.

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.

Symptom clusters in COVID-19: A potential clinical prediction tool from the COVID Symptom Study app.

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.

Aspirin Use and Risk of Colorectal Cancer Among Older Adults.

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.