Gastrointestinal Safety of Aspirin for a High-Dose, Multiple-Day Treatment Regimen: A Meta-Analysis of Three Randomized Controlled Trials

Background and Aim: Aspirin is a commonly used over-the-counter (OTC) agent for the symptomatic treatment of acute pain, fever, or the common cold, but data regarding safety in this context are limited. In order to characterize the safety of aspirin beyond single-dose or long-term use data, we conducted a meta-analysis of multiple-dose, multiple-day studies of OTC aspirin at a label-approved dosage. Methods: We conducted a meta-analysis of individual patient data from three Bayer-sponsored studies. The meta-analysis was performed in 2015; the individual studies were conducted between 2008 and 2012 and were of a randomized, parallel-group, placebo-controlled design. Patients received a minimum dosage of aspirin of 2000 mg/day over at least 3 days. The endpoints were patient-reported adverse events (AEs) with an emphasis on the system organ class gastrointestinal system. Event incidences were estimated and an analysis of the odds ratios (ORs) and risk differences (RDs) of aspirin versus placebo were performed. Results: Of the 819 patients included, 433 were treated with aspirin and 386 were treated with placebo. The majority of patients (85.7 %) received a median dose of aspirin of 3000 mg/day for 3 days. The incidence of the overall AEs was low and rates were comparable between the aspirin (10.9 %) and placebo (12.4 %) groups [OR: 0.86 (95 % confidence interval [CI] 0.56, 1.34); RD: -1.49 (95 % CI -6.01, 3.03)]. Gastrointestinal AEs were more common in subjects treated with aspirin (7.4 %) than with placebo (5.4 %), and although this difference did not reach statistical significance, a trend towards increased risk was observed with aspirin use [OR: 1.41 (95 % CI 0.78, 2.54); RD: 2.00 (95 % CI -1.35, 5.35)]. Nausea, upper abdominal pain, dyspepsia, and diarrhea were the most frequently reported gastrointestinal AEs. There were no reports of serious gastrointestinal complications such as bleeding, perforation, or ulceration.: Conclusions: The multiple-dose regimen of aspirin used for several days according to the OTC label is well-tolerated by otherwise healthy non-elderly subjects for short-term and symptomatic treatment of pain, fever, and the common cold. There were no reports of serious gastrointestinal complications in either of the groups

Colorectal cancer population screening programs worldwide in 2016: An update

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The incidence and mortality show wide geographical variations. Screening is recommended to reduce both incidence and mortality. However, there are significant differences among studies in implementation strategies and detection. This review aimed to present the results and strategies of different screening programs worldwide. We reviewed the literature on national and international screening programs published in PubMed, on web pages, and in clinical guidelines. CRC Screening programs are currently underway in most European countries, Canada, specific regions in North and South America, Asia, and Oceania. The most extensive screening strategies were based on fecal occult blood testing, and more recently, the fecal immunochemical test (FIT). Participation in screening has varied greatly among different programs. The Netherlands showed the highest participation rate (68.2%) and some areas of Canada showed the lowest (16%). Participation rates were highest among women and in programs that used the FIT test. Men exhibited the greatest number of positive results. The FIT test has been the most widely used screening program worldwide. The advent of this test has increased participation rates and the detection of positive results

Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199, 049 new users of low-dose aspirin (75-300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case-control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54-0.88) for >1 month PPI use and 2.65 (1.62-4.3) for 1 month PPI use and 1.12 (0.73-1.71) for 1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk

Incidence of Upper and Lower Gastrointestinal Bleeding in New Users of Low-Dose Aspirin

Background & Aims: There are few data on the incidence of upper and lower gastrointestinal bleeding (UGIB and LGIB) from observational studies of low-dose aspirin users. We aimed to estimate incidence rates of UGIB and LGIB in a large cohort of new users of low-dose aspirin in the United Kingdom, with subanalyses of hospitalization status and fatalities. Methods: We performed a population-based study of 199, 079 new users of low-dose aspirin (median age, 64.0 years) identified from the Health Improvement Network primary care database (2000–2012). Individuals were followed for a median 5.4 years (maximum, 14 years) to identify new cases of UGIB and LGIB. Following multistep validation, we calculated overall and age- and sex-specific incidence rates; we performed subanalyses for health care use and death within 30 days of GIB. We also estimated rates within a matched (1:1) cohort of nonusers of low-dose aspirin at the start of the follow-up period. Results: The low-dose aspirin users had 1115 UGIB events and 1936 LGIB events; most subjects with UGIB events (58.9%) were hospitalized, whereas most subjects with LGIB events were referred to secondary care (72.8%). Crude incidence rates of GIB per 1000 person-years were 0.97 for subjects with UGIB (95% CI, 0.91–1.02) and 1.68 for subjects with LGIB (95% CI, 1.60–1.75). Incidence rates per 1000 person-years for patients hospitalized for GIB were 0.57 for UGIB (95% CI, 0.53–0.61) and 0.45 for LGIB (95% CI, 0.42–0.49); for referred (but not hospitalized) cases, these values were 0.39 for UGIB (95% CI, 0.36–0.43) and 1.22 for LGIB (1.16–1.29). Incidence rates per 1000 person-years were 0.06 for fatal UGIB (95% CI, 0.04–0.07), 0.01 for fatal LGIB (95% CI, 0.01–0.02), 0.91 for nonfatal UGIB (95% CI, 0.86–0.97), and 1.66 for nonfatal LGIB (95% CI, 1.59–1.74). Among nonusers of low-dose aspirin, incidence rates per 1000 person-years were 0.67 (95% CI, 0.63–0.75) for UGIB and 0.76 (95% CI, 0.72–0.82) for LGIB. Conclusion: In a population-based study of low-dose aspirin users, the incidence of LGIB was higher than the incidence of UGIB. However, incidence rates of hospitalized GI bleeds and 30-day mortality rates were lower for LGIB than for UGIB. These estimates are valuable for benefit–risk assessments of low-dose aspirin for cardiovascular and colorectal cancer prevention

Faecal haemoglobin concentration, a good predictor of risk of advanced colorectal neoplasia in symptomatic and asymptomatic patients

Background: Periodical faecal immunochemical testing (FIT) is a cost-effective strategy in colon cancer screening programmes. FIT is also used as a diagnostic test in symptomatic patients. but data are scarce. Aim: To determine the association between FIT-Hb concentration and the risk of advanced neoplasia (AN) detected in colonoscopy in two different populations. Methods. The outcomes of colonoscopies performed after a positive FIT (> 117 ng/ml) (Sentinel Gold test) result were analysed in patients included within a population-based CRC screening programme (screening group) and, as diagnostic evaluation in symptomatic patients (symptomatic group). The study was performed between January 1st, 2014 and October 31, 2016. Data are reported Con as medians with interquartile ranges or frequencies and percentages. Positive predictive value (PPV) at arbitrary faecal haemoglobin concentrations were also reported calculated for AN. Results: We recruited 2742 patients who underwent a colonoscopy procedure, 1515 (53.5%) of them within the CRC screening programme. Patients in the screening group were younger (65.0±3.3 vs 66.2±13.4 years, p 1000 ng/ml) compared to those in the symptomatic group (36.3% - 52.5%). Similar trends were observed for cancer diagnosis alone. Conclusions: Male gender, age and FIT Hb concentration are predictors of risk of advanced adenoma and colorectal cancer and should be used to prioritise colonoscopy in patients with suspected advanced neoplasia, both in screening and in symptomatic patients

Blood-cell-based inflammatory markers as a useful tool for early diagnosis in colorectal cancer

Background: Systemic inflammation seems to be involved in the pathogenetic pathways of colorectal cancer (CRC). Analytical markers that reflect the inflammatory status, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or systemic immune-inflammation index (SII), have been proposed as tools for the prognosis of CRC. Nevertheless, their use for diagnosis has been scarcely investigated. Aims: To analyze the ability of these markers and of a new marker combining SII and hemoglobin concentration, named NP/LHb = neutrophils x platelets]/lymphocytes x hemoglobin], as tools for CRC diagnosis. Furthermore, we studied their association with CRC-related variables. Methods: Case-control study including 214 CRC patients and 214 controls without CRC, matched by age (±5 years) and sex. We collected demographic, CRC-related and laboratory variables to calculate NLR, PLR, SII, and NP/LHb. In the case group, the laboratory variables were collected at two different period times, 6 months (IQR 4–8) before the CRC diagnosis and at the time of the diagnosis. ROC analysis was performed to evaluate the discriminatory accuracy of each index and we calculated Se, Sp, PPV, NPV, and OR to identify the diagnostic performance of each positive marker. Results: NP/LHb showed high Sp (92.06%) and PPV (87.50%) to diagnose patients with CRC. This index exhibited an OR of 14.52 (8.26–25.52) and the best area under the curve (AUC: 0.78) for a positive CRC diagnosis. We found significant differences in all indices according to the presence of CRC, observing the highest values in CRC patients at time of diagnosis, in comparison with the analysis performed in the previous months to diagnosis or with control patients. There were significant differences in all ratios according to TNM stages (p < 0.05). PLR, SII and NP/LHb (but not NLR) showed significant differences according to tumor location (p < 0.05). Right-sided colon cancers presented the highest values, in comparison with left-sided and rectal cancers. Conclusions: Systemic inflammatory cell ratios (especially NP/LHb) change over time with the development of CRC, so they could be useful in its early diagnosis. We suggest that they could be routinely measured in patients with suspicion of CRC, to identify those ones with a higher risk of cancer, considering the high positive predictive value they have shown in our study. Copyright © 2022 Hernandez-Ainsa, Velamazan, Lanas, Carrera-Lasfuentes and Piazuelo

Deconvolution analysis for classifying gastric adenocarcinoma patients based on differential scanning calorimetry serum thermograms

Recently, differential scanning calorimetry (DSC) has been acknowledged as a novel tool for diagnosing and monitoring several diseases. This highly sensitive technique has been traditionally used to study thermally induced protein folding/unfolding transitions. In previous research papers, DSC profiles from blood samples of patients were analyzed and they exhibited marked differences in the thermal denaturation profile. Thus, we investigated the use of this novel technology in blood serum samples from 25 healthy subjects and 30 patients with gastric adenocarcinoma (GAC) at different stages of tumor development with a new multiparametric approach. The analysis of the calorimetric profiles of blood serum from GAC patients allowed us to discriminate three stages of cancer development (I to III) from those of healthy individuals. After a multiparametric analysis, a classification of blood serum DSC parameters from patients with GAC is proposed. Certain parameters exhibited significant differences (P < 0.05) and allowed the discrimination of healthy subjects/patients from patients at different tumor stages. The results of this work validate DSC as a novel technique for GAC patient classification and staging, and offer new graphical tools and value ranges for the acquired parameters in order to discriminate healthy from diseased subjects with increased disease burden

Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds - Gastrointestinal adverse effects: A meta-analysis of randomized clinical trials

Background and Aim: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over-the-counter drug for the treatment of pain, fever, or colds, but data on the safety of this use are very limited. The aim of this study was to provide data on the safety of this treatment pattern, which is of interest to clinicians, regulators, and the public. Methods: A meta-analysis of individual patient data from 67 studies sponsored by Bayer HealthCare was completed. The primary endpoints were patient-reported gastrointestinal (GI) adverse events (AEs); the secondary endpoints were the incidence of patient-reported non-GI AEs. Event incidence and odds ratios (ORs) based on Cochran-Mantel-Haenszel estimates are reported. In total, 6181 patients were treated with ASA, 3515 with placebo, 1145 with acetaminophen (paracetamol), and 754 with ibuprofen. Exposure to ASA was short term (82.5% of patients had a single dose). Results: GI AEs were more frequent with ASA (9.9%) than with placebo (9.0%) [OR 1.3; 95% CI 1.1, 1.5]. Dyspeptic symptoms were infrequent (4.6% in placebo subjects). The ORs for ASA were 1.3 (95% CI 1.1, 1.6) versus placebo; 1.55 (95% CI 0.7, 3.3) versus ibuprofen; and 1.04 (95% CI 0.8, 1.4) versus acetaminophen. There were very few serious GI AEs (one ASA case; three placebo cases). No differences were found for non-GI AEs and no cases of cerebral hemorrhage were reported. Conclusion: Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo.No serious GI complications were reported

Management of iron-deficiency anemia following acute gastrointestinal hemorrhage: A narrative analysis and review

Many patients experiencing acute gastrointestinal bleeding (GIB) require iron supplemen-tation to treat subsequent iron deficiency (ID) or iron-deficiency anemia (IDA). Guidelinesregarding management of these patients are lacking. We aimed to identify areas of unmetneed in patients with ID/IDA following acute GIB in terms of patient management andphysician guidance. We formed an international working group of gastroenterologists toconduct a narrative review based on PubMed and EMBASE database searches (fromJanuary 2000 to February 2021), integrated with observations from our own clinical expe-rience. Published data on this subject are limited and disparate, and those relating topost-discharge outcomes, such as persistent anemia and re-hospitalization, are particularlylacking. Often, there is no post-discharge follow-up of these patients by a gastroenterolo-gist. Acute GIB-related ID/IDA, however, is a prevalent condition both at the time of hos-pital admission and at hospital discharge and is likely underdiagnosed and undertreated.Despite limited data, there appears to be notable variation in the prescribing of intravenous(IV)/oral iron regimens. There is also some evidence suggesting that, compared with oraliron, IV iron may restore iron levels faster following acute GIB, have a better tolerabilityprofile, and be more beneficial in terms of quality of life. Gaps in patient care exist inthe management of acute GIB-related ID/IDA, yet further data from largepopulation-based studies are needed to confirm this. We advocate the formulation ofevidence-based guidance on the use of iron therapies in these patients, aiding a more stan-dardized best-practice approach to patient care

Evidence-based selection on the appropriate FIT cut-off point in CRC screening programs in the COVID pandemic

Background: The COVID pandemic has forced the closure of many colorectal cancer (CRC) screening programs. Resuming these programs is a priority, but fewer colonoscopies may be available. We developed an evidence-based tool for decision-making in CRC screening programs, based on a fecal hemoglobin immunological test (FIT), to optimize the strategy for screening a population for CRC. Methods: We retrospectively analyzed data collected at a regional CRC screening program between February/2014 and November/2018. We investigated two different scenarios: not modifying vs. modifying the FIT cut-off value. We estimated program outcomes in the two scenarios by evaluating the numbers of cancers and adenomas missed or not diagnosed in due time (delayed). Results: The current FIT cut-off (20-mu g hemoglobin/g feces) led to 6, 606 colonoscopies per 100, 000 people invited annually. Without modifying this FIT cut-off value, when the optimal number of individuals invited for colonoscopies was reduced by 10-40%, a high number of CRCs and high-risk adenomas (34-135 and 73-288/100.000-people invited, respectively) will be undetected every year. When the FIT cut-off value was increased to where the colonoscopy demand matched the colonoscopy availability, the number of missed lesions per year was remarkably reduced (9-36 and 29-145/100.000 people, respectively). Moreover, the unmodified FIT scenario outcome was improved by prioritizing the selection process based on sex (males) and age, rather than randomly reducing the number invited. Conclusions: Assuming a mismatch between the availability and demand for annual colonoscopies, increasing the FIT cut-off point was more effective than randomly reducing the number of people invited. Using specific risk factors to prioritize access to colonoscopies should be also considered