It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin.
To test that continuing ...aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases.
A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725)
A tertiary endoscopy center.
Low-dose aspirin recipients with peptic ulcer bleeding.
78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up.
The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks.
156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points 95% CI, -3.6 to 13.4 percentage points). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points CI, 3.7 to 19.5 percentage points). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points CI, 1.7 to 16.3 percentage points).
The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy.
Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.
Flexible and self‐powered photodetectors (PDs) are highly desirable for applications in image sensing, smart building, and optical communications. In this paper, a self‐powered and flexible PD based ...on the methylammonium lead iodide (CH3NH3PBI3) perovskite is demonstrated. Such a self‐powered PD can operate even with irregular motion such as human finger tapping, which enables it to work without a bulky external power source. In addition, with high‐quality CH3NH3PBI3 perovskite thin film fabricated with solvent engineering, the PD exhibits an impressive detectivity of 1.22 × 1013 Jones. In the self‐powered voltage detection mode, it achieves a large responsivity of up to 79.4 V mW−1 cm−2 and a voltage response of up to ≈90%. Moreover, as the PD is made of flexible and transparent polymer films, it can operate under bending and functions at 360 ° of illumination. As a result, the self‐powered, flexible, 360 ° omnidirectional perovskite PD, featuring high detectivity and responsivity along with real‐world sensing capability, suggests a new direction for next‐generation optical communications, sensing, and imaging applications.
A flexible and self‐powered organometallic halide perovskite photodetector is demonstrated that features an impressive detectivity of 1.22 × 1013 Jones and a large responsivity of up to 79.4 V mW−1 cm2. These results demonstrate a promising approach for developing a flexible and self‐powered photodetector featuring high detectivity, responsivity, and excellent compatibility in various situations, particularly for outdoor applications.
The lung comprises an extensive surface of epithelia constantly exposed to environmental insults. Maintaining the integrity of the alveolar epithelia is critical for lung function and gaseous ...exchange. However, following severe pulmonary damage, what progenitor cells give rise to alveolar type I and II cells during the regeneration of alveolar epithelia has not been fully determined. In this study, we have investigated this issue by using transgenic mice in which Scgb1a1-expressing cells and their progeny can be genetically labeled with EGFP. We show that following severe alveolar damage induced either by bleomycin or by infection with influenza virus, the majority of the newly generated alveolar type II cells in the damaged parenchyma were labeled with EGFP. A large proportion of EGFP-expressing type I cells were also observed among the type II cells. These findings strongly suggest that Scgb1a1-expressing cells, most likely Clara cells, are a major cell type that gives rise to alveolar type I and II cells during the regeneration of alveolar epithelia in response to severe pulmonary damage in mice.
Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who ...have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients.
We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding.
We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001).
Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.
Regeneration of alveolar epithelia following severe pulmonary damage is critical for lung function. We and others have previously shown that Scgb1a1-expressing cells, most likely Clara cells, can ...give rise to newly generated alveolar type 2 cells (AT2s) in response to severe lung damage induced by either influenza virus infection or bleomycin treatment. In this study, we have investigated cellular pathway underlying the Clara cell to AT2 differentiation. We show that the initial intermediates are bronchiolar epithelial cells that exhibit Clara cell morphology and express Clara cell marker, Scgb1a1, as well as the AT2 cell marker, pro-surfactant protein C (pro-SPC). These cells, referred to as pro-SPC(+) bronchiolar epithelial cells (or SBECs), gradually lose Scgb1a1 expression and give rise to pro-SPC(+) cells in the ring structures in the damaged parenchyma, which appear to differentiate into AT2s via a process sharing some features with that observed during alveolar epithelial development in the embryonic lung. These findings suggest that SBECs are intermediates of Clara cell to AT2 differentiation during the repair of alveolar epithelia following severe pulmonary injury.
Current guidelines recommend that patients at risk for ulcer disease who require treatment for arthritis receive nonsteroidal antiinflammatory drugs (NSAIDs) that are selective for cyclooxygenase-2 ...or the combination of a nonselective NSAID with a proton-pump inhibitor. We assessed whether celecoxib would be similar to diclofenac plus omeprazole in reducing the risk of recurrent ulcer bleeding in patients at high risk for bleeding.
We studied patients who used NSAIDs for arthritis and who presented with ulcer bleeding. After their ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 200 mg of celecoxib twice daily plus daily placebo or 75 mg of diclofenac twice daily plus 20 mg of omeprazole daily for six months. The end point was recurrent ulcer bleeding.
In the intention-to-treat analysis, which included 287 patients (144 receiving celecoxib and 143 receiving diclofenac plus omeprazole), recurrent ulcer bleeding occurred in 7 patients receiving celecoxib and 9 receiving diclofenac plus omeprazole. The probability of recurrent bleeding during the six-month period was 4.9 percent (95 percent confidence interval, 3.1 to 6.7) for patients who received celecoxib and 6.4 percent (95 percent confidence interval, 4.3 to 8.4) for patients who received diclofenac plus omeprazole (difference, -1.5 percentage points; 95 percent confidence interval for the difference, -6.8 to 3.8). Renal adverse events, including hypertension, peripheral edema, and renal failure, occurred in 24.3 percent of the patients receiving celecoxib and 30.8 percent of those receiving diclofenac plus omeprazole.
Among patients with a recent history of ulcer bleeding, treatment with celecoxib was as effective as treatment with diclofenac plus omeprazole, with respect to the prevention of recurrent bleeding. Renal toxic effects are common in high-risk patients receiving celecoxib or diclofenac plus omeprazole.
Neuromuscular electrical stimulation (NMES) is extensively used in stroke motor rehabilitation. How it promotes motor recovery remains only partially understood. NMES could change muscular ...properties, produce altered sensory inputs, and modulate fluctuations of cortical activities; but the potential contribution from cortico-muscular couplings during NMES synchronized with dynamic movement has rarely been discussed.
We investigated cortico-muscular interactions during passive, active, and NMES rhythmic pedaling in healthy subjects and chronic stroke survivors. EEG (128 channels), EMG (4 unilateral lower limb muscles) and movement parameters were measured during 3 sessions of constant-speed pedaling. Sensory-level NMES (20 mA) was applied to the muscles, and cyclic stimulation patterns were synchronized with the EMG during pedaling cycles. Adaptive mixture independent component analysis was utilized to determine the movement-related electro-cortical sources and the source dipole clusters. A directed cortico-muscular coupling analysis was conducted between representative source clusters and the EMGs using generalized partial directed coherence (GPDC). The bidirectional GPDC was compared across muscles and pedaling sessions for post-stroke and healthy subjects.
Directed cortico-muscular coupling of NMES cycling was more similar to that of active pedaling than to that of passive pedaling for the tested muscles. For healthy subjects, sensory-level NMES could modulate GPDC of both ascending and descending pathways. Whereas for stroke survivors, NMES could modulate GPDC of only the ascending pathways.
By clarifying how NMES influences neuromuscular control during pedaling in healthy and post-stroke subjects, our results indicate the potential limitation of sensory-level NMES in promoting sensorimotor recovery in chronic stroke survivors.
Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the ...clinical outcomes of COVID-19 among vaccine recipients.
This was a territory-wide cohort study of 3 272 286 vaccine recipients (aged ≥ 18 years) of ≥ 2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID-19. The primary outcome was COVID-19, and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre-vaccination PPI use (any prescription within 90 days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use.
Among 439 154 PS-matched two-dose vaccine recipients (mean age: 65.3 years; male: 45.7%) with a median follow-up of 6.8 months (interquartile range: 2.6-7.9), PPI exposure was associated with a higher risk of COVID-19 (aIRR: 1.08; 95% confidence interval 95% CI: 1.05-1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08-1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24-1.98). Among 188 360 PS-matched three-dose vaccine recipients (mean age: 62.5 years; male: 49.0%; median follow-up: 9.1 months interquartile range: 8.0-10.9), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08-1.15) but not other outcomes.
Although PPI use was associated with a higher COVID-19 risk, severe infection was limited to two-dose but not three-dose vaccine recipients.
Background & Aims Inflammatory bowel diseases (IBD) are becoming more common in Asia, but epidemiologic data are lacking. The Asia-Pacific Crohn’s and Colitis Epidemiology Study aimed to determine ...the incidence and phenotype of IBD in 8 countries across Asia and in Australia. Methods We performed a prospective, population-based study of IBD incidence in predefined catchment areas, collecting data for 1 year, starting on April 1, 2011. New cases were ascertained from multiple overlapping sources and entered into a Web-based database. Cases were confirmed using standard criteria. Local endoscopy, pathology, and pharmacy records were searched to ensure completeness of case capture. Results We identified 419 new cases of IBD (232 of ulcerative colitis UC, 166 of Crohn’s disease CD, and 21 IBD-undetermined). The crude annual overall incidence values per 100,000 individuals were 1.37 for IBD in Asia (95% confidence interval: 1.25−1.51; 0.76 for UC, 0.54 for CD, and 0.07 for IBD-undetermined) and 23.67 in Australia (95% confidence interval: 18.46−29.85; 7.33 for UC, 14.00 for CD, and 2.33 for IBD-undetermined). China had the highest incidence of IBD in Asia (3.44 per 100,000 individuals). The ratios of UC to CD were 2.0 in Asia and 0.5 in Australia. Median time from symptom onset to diagnosis was 5.5 months (interquartile range, 1.4−15 months). Complicated CD (stricturing, penetrating, or perianal disease) was more common in Asia than Australia (52% vs 24%; P = .001), and a family history of IBD was less common in Asia (3% vs 17%; P < .001). Conclusions We performed a large-scale population-based study and found that although the incidence of IBD varies throughout Asia, it is still lower than in the West. IBD can be as severe or more severe in Asia than in the West. The emergence of IBD in Asia will result in the need for specific health care resources, and offers a unique opportunity to study etiologic factors in developing nations.
Background: Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of ...COVID-19 vaccine recipients. Methods: This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged ≥ 18 years) with ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior COVID-19, prior gastrointestinal surgery, and immunocompromised status. The primary outcome was COVID-19 infection and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Exposure was pre-vaccination antibiotic use (within 180 days of first vaccine dose). Covariates included age, sex, Charlson Comorbidity Index, and concomitant medication use. Subjects were followed from the index date (first dose vaccination) until outcome occurrence, death, an additional dose of vaccination, or 15 November 2022. Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with antibiotic use. Results: Among 342,338 PS matched three-dose vaccine recipients (mean age: 57.4 years; male: 45.1%) with a median follow-up of 13.6 months (IQR: 9.2–16.3), antibiotics were associated with a higher risk of COVID-19 infection (aIRR: 1.16;95% CI: 1.14–1.19), hospitalization (aIRR: 1.75;95% CI: 1.65–1.86), and severe infection (aIRR: 1.60; 95% CI: 1.21–2.11). Notably, antibiotic use was associated with a higher risk of severe infection and death among CoronaVac recipients (aIRR: 1.62 95% CI: 1.18–2.22 and aIRR: 2.70, 95% CI: 1.54–4.73 for the two secondary outcomes, respectively), but not BNT162b2 recipients. Conclusions: Pre-vaccination use of antibiotics was associated with a higher risk of COVID-19 infection, hospitalization, and severe disease outcomes.
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