Low-Dose Aspirin and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway.

INTRODUCTION: To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC). METHODS: In this nationwide cohort study, we identified individuals aged 50 years or older residing for 6 months or more in Norway in 2004-2018 and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk. In addition, we calculated the number of CRC potentially averted by low-dose aspirin use. RESULTS: We included 2,186,390 individuals. During the median follow-up of 10.9 years, 579,196 (26.5%) used low-dose aspirin, and 38,577 (1.8%) were diagnosed with CRC. Current use of aspirin vs never use was associated with lower CRC risk (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.84-0.90). The association was more pronounced for metastatic CRC (HR 0.79; 95% CI 0.74-0.84) than regionally advanced (HR 0.89; 95% CI 0.85-0.92) and localized CRC (HR 0.93; 95% CI 0.87-1.00; P heterogeneity = 0.001). A significant trend was found between duration of current use and CRC risk: HR 0.91 (95% CI 0.86-0.95) for <3 years, HR 0.85 (0.80-0.91) for ≥3 and <5 years, and HR 0.84 (0.80-0.88) for ≥5 years of use vs never use ( P trend < 0.001). For past use, HR were 0.89 (95% CI 0.84-0.94) for <3 years, 0.90 (0.83-0.99) for ≥3 and <5 years, and 0.98 (0.91-1.06) for ≥5 years since last use vs never use ( P -trend < 0.001). We estimated that aspirin use averted 1,073 cases of CRC (95% CI 818-1,338) in the study period. DISCUSSION: In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.

Informant-based screening tools for dementia: an overview of systematic reviews.

BACKGROUND: Informant-based questionnaires may have utility for cognitive impairment or dementia screening. Reviews describing the accuracy of respective questionnaires are available, but their focus on individual questionnaires precludes comparisons across tools. We conducted an overview of systematic reviews to assess the comparative accuracy of informant questionnaires and identify areas where evidence is lacking. METHODS: We searched six databases to identify systematic reviews describing diagnostic test accuracy of informant questionnaires for cognitive impairment or dementia. We pooled sensitivity and specificity data for each questionnaire and used network approaches to compare accuracy estimates across the differing tests. We used grading of recommendations, assessment, development and evaluation (GRADE) to evaluate the overall certainty of evidence. Finally, we created an evidence 'heat-map', describing the availability of accurate data for individual tests in different populations and settings. RESULTS: We identified 25 reviews, consisting of 93 studies and 13 informant questionnaires. Pooled analysis (37 studies; 11 052 participants) ranked the eight-item interview to ascertain dementia (AD8) highest for sensitivity [90%; 95% credible intervals (CrI) = 82-95; 'best-test' probability = 36]; while the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) was most specific (81%; 95% CrI = 66-90; 'best-test' probability = 29%). GRADE-based evaluation of evidence suggested certainty was 'low' overall. Our heat-map indicated that only AD8 and IQCODE have been extensively evaluated and most studies have been in the secondary care settings. CONCLUSIONS: AD8 and IQCODE appear to be valid questionnaires for cognitive impairment or dementia assessment. Other available informant-based cognitive screening questionnaires lack evidence to justify their use at present. Evidence on the accuracy of available tools in primary care settings and with specific populations is required.

Low-dose aspirin and risk of breast cancer: a Norwegian population-based cohort study of one million women.

Several studies evaluated the association between aspirin use and risk of breast cancer (BC), with inconsistent results. We identified women aged ≥ 50 years residing in Norway between 2004 and 2018, and linked data from nationwide registries; including the Cancer Registry of Norway, the Norwegian Prescription Database, and national health surveys. We used Cox regression models to estimate the association between low-dose aspirin use and BC risk, overall and by BC characteristics, women's age and body mass index (BMI), adjusting for sociodemographic factors and use of other medications. We included 1,083,629 women. During a median follow-up of 11.6 years, 257,442 (24%) women used aspirin, and 29,533 (3%) BCs occurred. For current use of aspirin, compared to never use, we found an indication of a reduced risk of oestrogen receptor-positive (ER +) BC (hazard ratio [HR] = 0.96, 95% confidence interval [CI]: 0.92-1.00), but not ER-negative BC (HR = 1.01, 95%CI: 0.90-1.13). The association with ER + BC was only found in women aged ≥ 65 years (HR = 0.95, 95%CI: 0.90-0.99), and became stronger as the duration of use increased (use of ≥ 4 years HR = 0.91, 95%CI: 0.85-0.98). BMI was available for 450,080 (42%) women. Current use of aspirin was associated with a reduced risk of ER + BC in women with BMI ≥ 25 (HR = 0.91, 95%CI: 0.83-0.99; HR = 0.86, 95%CI: 0.75-0.97 for use of ≥ 4 years), but not in women with BMI < 25.Use of low-dose aspirin was associated with reduced risk of ER + BC, in particular in women aged ≥ 65 years and overweight women.

Association between use of low-dose aspirin and detection of colorectal polyps and cancer in a screening setting.

BACKGROUND: The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated. METHODS: We used data from Bowel Cancer Screening in Norway, a trial randomizing individuals from general population, aged 50-74 years, to flexible sigmoidoscopy or faecal immunochemical test (FIT), to study the association between aspirin use and detection of CRC and two CRC precursors: adenomas and advanced serrated lesions (ASL). Prescriptions of low-dose aspirin were obtained from Norwegian prescription database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 64,889 screening participants (24,159 sigmoidoscopy, 40,730 FIT), 314 (0.5%) had CRC, 6,208 (9.6%) adenoma and 659 (1.0%) ASL. Overall and short-term use (<3 years) of low-dose aspirin, versus no use, were not associated with any colorectal lesion. Long-term use (≥3 years) was associated with lower detection of CRC (overall OR 0.66, 95%CI 0.46-0.93; sigmoidoscopy: 0.56, 0.33-0.97; FIT: 0.72, 0.45-1.15), adenomas in sigmoidoscopy arm (overall OR 0.95, 95%CI 0.87-1.03; sigmoidoscopy: 0.89, 0.80-0.99; FIT: 1.03, 0.89-1.18), but not ASLs. We did not observe significant differences in the effect of aspirin according to the location of colorectal lesions. CONCLUSION: Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs.

Application of Magnetic Resonance Imaging in Liver Biomechanics: A Systematic Review.

MRI-based biomechanical studies can provide a deep understanding of the mechanisms governing liver function, its mechanical performance but also liver diseases. In addition, comprehensive modeling of the liver can help improve liver disease treatment. Furthermore, such studies demonstrate the beginning of an engineering-level approach to how the liver disease affects material properties and liver function. Aimed at researchers in the field of MRI-based liver simulation, research articles pertinent to MRI-based liver modeling were identified, reviewed, and summarized systematically. Various MRI applications for liver biomechanics are highlighted, and the limitations of different viscoelastic models used in magnetic resonance elastography are addressed. The clinical application of the simulations and the diseases studied are also discussed. Based on the developed questionnaire, the papers' quality was assessed, and of the 46 reviewed papers, 32 papers were determined to be of high-quality. Due to the lack of the suitable material models for different liver diseases studied by magnetic resonance elastography, researchers may consider the effect of liver diseases on constitutive models. In the future, research groups may incorporate various aspects of machine learning (ML) into constitutive models and MRI data extraction to further refine the study methodology. Moreover, researchers should strive for further reproducibility and rigorous model validation and verification.

Informant-based screening tools for diagnosis of dementia, an overview of systematic reviews of test accuracy studies protocol.

BACKGROUND: Robust diagnosis of dementia requires an understanding of the accuracy of the available diagnostic tests. Informant questionnaires are frequently used to assess for dementia in clinical practice. Recent systematic reviews have sought to establish the diagnostic test accuracy of various dementia informant screening tools. However, most reviews to date have focused on a single diagnostic tool and this does not address which tool is 'best'. A key aim of the overview of systematic reviews is to present a disparate evidence base in a single, easy to access platform. METHODS: We will conduct an overview of systematic reviews in which we 'review the systematic reviews' of diagnostic test accuracy studies evaluating informant questionnaires for dementia. As an overview of systematic reviews of test accuracy is a relatively novel approach, we will use this review to explore methods for visual representation of complex data, for highlighting evidence gaps and for indirect comparative analyses. We will create a list of informant tools by consulting with dementia experts. We will search 6 databases (EMBASE (OVID); Health and Psychosocial Instruments (OVID); Medline (OVID); CINAHL (EBSCO); PSYCHinfo (EBSCO) and the PROSPERO registry of review protocols) to identify systematic reviews that describe the diagnostic test accuracy of informant questionnaires for dementia. We will assess review quality using the AMSTAR-2 (Assessment of Multiple Systematic Reviews) and assess reporting quality using PRISMA-DTA (Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies) checklists. We will collate the identified reviews to create an 'evidence map' that highlights where evidence does and does not exist in relation to informant questionnaires. We will pool sensitivity and specificity data via meta-analysis to generate a diagnostic test accuracy summary statistic for each informant questionnaire. If data allow, we will perform a statistical comparison of the diagnostic test accuracy of each informant questionnaire using a network approach. DISCUSSION: Our overview of systematic reviews will provide a concise summary of the diagnostic test accuracy of informant tools and highlight areas where evidence is currently lacking in this regard. It will also apply network meta-analysis techniques to a new area.

Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen-induced toxicity in isolated rat hepatocytes.

Acetaminophen (N-acetyl para amino phenol, APAP) is a widely used antipyretic and analgesic drug responsible for various drug-induced liver injuries. This study evaluated APAP-induced toxicity in isolated rat hepatocytes alongside the protective effects of silafibrate and N-acetyl cysteine (NAC). Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via the portal vein. This technique is based on liver perfusion with collagenase after removing calcium ions (Ca2+) with a chelator. Cells were treated with different concentrations of APAP, silafibrate, and NAC. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial depolarisation were measured as toxicity markers. ROS formation and lipid peroxidation occurred after APAP administration to rat hepatocytes. APAP caused mitochondrial depolarisation in isolated cells. Administration of silafibrate (200 µmol L-1) and/or NAC (200 µmol L-1) reduced the ROS formation, lipid peroxidation, and mitochondrial depolarisation caused by APAP. Cytotoxicity induced by APAP in rat hepatocytes was mediated by oxidative stress. In addition, APAP seemed to target cellular mitochondria during hepatocyte damage. The protective properties of silafibrate and/or NAC against APAP­induced hepatic injury may have involved the induction of antioxidant enzymes, protection against oxidative stress and inflammatory responses, and alteration in cellular glutathione content.