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Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.
Middha, P, Thummalapalli, R, Betti, MJ, Yao, L, Quandt, Z, Balaratnam, K, Bejan, CA, Cardenas, E, Falcon, CJ, Faleck, DM, et al
Nature communications. 2024;(1):2568
Abstract
Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12-1.64, P = 2×10-03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18-1.88, P = 9×10-04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07-4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.
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Association of statin and/or renin-angiotensin-aldosterone system modulating therapy with mortality in adults with diabetes admitted to hospital with COVID-19: A retrospective multicentre European study.
Harris, S, Ruan, Y, Wild, SH, Wargny, M, Hadjadj, S, Delasalle, B, Saignes, M, Ryder, RE, Field, BCT, Narendran, P, et al
Diabetes & metabolic syndrome. 2022;(5):102484
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Abstract
BACKGROUND & AIMS To assess the impact of pre-admission renin-angiotensin-aldosterone system inhibitor (RAASi) and statin use on mortality following COVID-19 hospitalization in adults with pre-existing diabetes. METHODS Retrospective cohort study of adults with diabetes admitted to ninety-nine participating hospitals in the United Kingdom, France and Spain during the first wave of the COVID-19 pandemic. Logistic regression models adjusted for demographic factors and comorbidity were used to describe associations with mortality in hospital or within 28 days of admission and individual or combined RAASi and statin therapy prescription followed by a country level meta-analysis. RESULTS Complete data were available for 3474 (42.6%) individuals. Prescribing patterns varied by country: 25-50% neither RAASi nor statin therapy, 14-36% both RAASi and statin therapy, 9-24% RAASi therapy alone, 12-36% statin alone. Overall, 20-37% of patients died within 28 days. Meta-analysis found no evidence of an association between mortality and prescription of RAASi therapy (OR 1.09, CI 0.78-1.52 (I2 22.2%)), statin (OR 0.97, CI 0.59-1.61 (I2 72.9%)) or both (OR 1.14, CI 0.67-1.92 (I2 78.3%)) compared to those prescribed neither drug class. CONCLUSIONS This large multicentre, multinational study found no evidence of an association between mortality from COVID-19 infection in people with diabetes and use of either RAASi, statin or combination therapy. This provides reassurance that clinicians should not change their RAASi and statin therapy prescribing practice in people with diabetes during the COVID-19 pandemic.
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Systematic review and meta-analysis examining the relationship between postprandial hypotension, cardiovascular events, and all-cause mortality.
Jenkins, DJA, Sahye-Pudaruth, S, Khodabandehlou, K, Liang, F, Kasmani, M, Wanyan, J, Wang, M, Selvaganesh, K, Paquette, M, Patel, D, et al
The American journal of clinical nutrition. 2022;(3):663-671
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Abstract
BACKGROUND Postprandial hypotension (PPH) has been reported to be associated with syncope, falls, adverse cardiovascular outcomes, and increased all-cause mortality. It has been reported to have an incidence as high as 30% in the elderly and persons with diabetes. We therefore performed a meta-analysis to determine the relation of PPH with cardiovascular disease (CVD) events and all-cause mortality. OBJECTIVES Our objective was to conduct a systematic review and meta-analysis of cohort and cross-sectional studies to determine the association of PPH with CVD and all-cause mortality. METHODS We searched the databases MEDLINE, EMBASE, and Cochrane library up to 13 April 2022 for prospective cohort and cross-sectional studies that examined the association of PPH with CVD outcomes and all-cause mortality. Data were analyzed using the generic inverse variance method with a random-effects model. Grading of Recommendations, Assessment, Development, and Evaluation approach assessed the certainty of evidence. RESULTS Seven studies that included 2389 participants met our inclusion criteria. PPH was associated with each outcome individually, including increased all-cause mortality, total CVD, CVD mortality, and stroke. CVD outcomes and all-cause mortality combined were also associated with PPH (RR: 1.52; 95% CI: 1.05, 2.18; P = 0.03; I2 = 77%). The certainty of evidence was graded as very low due to significant heterogeneity and the limited number of studies. CONCLUSIONS This assessment indicates an association of PPH with CVD and all-cause mortality. Further studies are required to improve CVD and mortality estimates, but the potential seriousness of CVD and all-cause mortality as outcomes of PPH justifies more screening, diagnosis, and research.
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Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.
Jenkins, DJA, Spence, JD, Giovannucci, EL, Kim, YI, Josse, RG, Vieth, R, Sahye-Pudaruth, S, Paquette, M, Patel, D, Blanco Mejia, S, et al
Journal of the American College of Cardiology. 2021;(4):423-436
Abstract
This is an update of the previous 2018 systematic review and meta-analysis of vitamin and mineral supplementation on cardiovascular disease outcomes and all-cause mortality. New randomized controlled trials and meta-analyses were identified by searching the Cochrane library, Medline, and Embase, and data were analyzed using random effects models and classified by the Grading of Recommendations Assessment Development and Evaluation approach. This updated review shows similar findings to the previous report for preventive benefits from both folic acid and B vitamins for stroke and has been graded with moderate quality. No effect was seen for the commonly used multivitamins, vitamin D, calcium, and vitamin C, and an increased risk was seen with niacin (with statin) for all-cause mortality. Conclusive evidence for the benefit of supplements across different dietary backgrounds, when the nutrient is sufficient, has not been demonstrated.
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Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.
Jenkins, DJA, Kitts, D, Giovannucci, EL, Sahye-Pudaruth, S, Paquette, M, Blanco Mejia, S, Patel, D, Kavanagh, M, Tsirakis, T, Kendall, CWC, et al
The American journal of clinical nutrition. 2020;112(6):1642-1652
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Plain language summary
Oxidative damage is a shared characteristic in chronic diseases such as cardiovascular disease (CVD), diabetes, cancer and ageing. Antioxidants mitigate the impact of oxidants and have been widely investigated in ageing and disease. However, the evidence for supplementary antioxidants has been mixed and some authorities have advised against the use of certain single nutrients for the prevention of CVD or cancer. This systematic review and meta-analysis focused on selenium due to its vital role in the antioxidant system and associations of low selenium blood levels with increased risk of CVD, cancers and death. The study included 43 randomised controlled trials (RCTs) evaluating the effect of supplemental selenium and antioxidants with or without selenium and their impact on CVD risk, cancer and all-cause mortality. Overall supplemental selenium or antioxidants alone did not seem to be associated with CVD outcomes, cancer, CVD and cancer mortality, or all-cause mortality. On close examination, a decreased risk was seen for CVD mortality when antioxidants were combined with selenium, whilst antioxidant mixtures without selenium demonstrated an increased risk in all-cause mortality. The findings did not seem to be influenced by dietary selenium intake. The authors suggested that inclusion of selenium as part of an antioxidant mix could be key for an antioxidant associated risk reduction. However, in the absence of further long term studies, a balanced antioxidant-rich diet was advocated as the safest approach. In clinical practice, where antioxidant support beyond diet is warranted, supplemental antioxidant use should be concurrent with adequate selenium supplementation, with dose benefits of 50-200mcg observed.
Abstract
BACKGROUND Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. OBJECTIVE We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. METHODS We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). CONCLUSION The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.
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Supplemental Vitamins and Minerals for CVD Prevention and Treatment.
Jenkins, DJA, Spence, JD, Giovannucci, EL, Kim, YI, Josse, R, Vieth, R, Blanco Mejia, S, Viguiliouk, E, Nishi, S, Sahye-Pudaruth, S, et al
Journal of the American College of Cardiology. 2018;(22):2570-2584
Abstract
The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.
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Thyroid Cancer and Nonsteroidal Anti-Inflammatory Drug Use: A Pooled Analysis of Patients Older Than 40 Years of Age.
Patel, D, Kitahara, CM, Park, Y, Liao, LM, Linet, M, Kebebew, E, Nilubol, N
Thyroid : official journal of the American Thyroid Association. 2015;(12):1355-62
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Abstract
BACKGROUND Cyclooxygenase (COX-2) has been associated with tumor growth and metastasis in several cancers, including thyroid cancer. For this reason, several investigators have studied COX-2 inhibitors in preclinical models of thyroid cancer and found antineoplastic effects. Thus, the primary aim of this study was to assess if the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of thyroid cancer. A second aim of the study was to determine additional risk or protective factors for thyroid cancer. METHODS Three large prospective population-based studies (the NIH-AARP Diet and Health Study; the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and the U.S. Radiologic Technologists Study) were pooled to investigate the association between self-reported frequency of aspirin and nonaspirin NSAID use one year prior to baseline (no use, ≤ 2/week, >2-6/week, and ≥ 7/week) and subsequent risk of thyroid cancer. A Cox regression proportional hazard model was used to estimate aggregated hazard ratios (HR) adjusted for cohort, sex, race/ethnicity, weight, smoking status, and alcohol intake. RESULTS There were 388,577 participants in the pooled cohort, with 481 cases of thyroid cancer. No significant risk reduction was observed with regular use of nonaspirin NSAIDs (HR = 1.14 [confidence interval (CI) 0.84-1.55]), and/or regular use of aspirin (HR = 1.06 [CI 0.82-1.39]). The multivariate regression analysis confirmed as previously reported in the literature that female sex, obesity class I (body mass index [BMI] = 30-34.99 kg/m(2)), and obesity class II (BMI = 35-35.99 kg/m(2)) were independently associated with an increased thyroid cancer risk. Current smoking status and moderate and excessive alcohol use were also confirmed as independent risk factors associated with a reduced thyroid cancer risk. CONCLUSIONS Neither nonaspirin NSAIDs nor aspirin use is associated with a reduced risk of thyroid cancer. Women and obesity are associated with an increased risk of thyroid cancer, whereas smoking and alcohol use are associated with decreased risk of thyroid cancer.
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Meta-analysis of the effects of lifestyle modifications on coronary and carotid atherosclerotic burden.
Jhamnani, S, Patel, D, Heimlich, L, King, F, Walitt, B, Lindsay, J
The American journal of cardiology. 2015;(2):268-75
Abstract
Lifestyle modifications are the crux of atherosclerotic disease management. The goal of this study was to determine the effectiveness of diet and exercise in decreasing coronary and carotid atherosclerotic burden. Randomized controlled trials examining the effects of intensive lifestyle measures on atherosclerotic progression in coronary and carotid arteries as measured by baseline and follow-up quantitative coronary angiogram and ultrasonographic carotid intimal-medial thickness (CIMT), respectively, were included. Studies were excluded if the intervention additionally included a medication. MEDLINE, EMBASE, CINAHL, Cochrane Controlled Trials Registers, reports, and abstracts from major cardiology meetings were searched by 2 researchers independently and verified by the primary investigator. Standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated using random-effects model. Publication bias and heterogeneity were assessed. Fourteen trials were included. Seven used quantitative coronary angiogram, and 7 used CIMT; 1,343 lesions in 340 patients in the coronary group and 919 patients in the carotid group were analyzed. Overall, lifestyle modifications were associated with a decrease in coronary atherosclerotic burden in percent stenosis by -0.34 (95% CI -0.48 to -0.21) SMD, with no significant publication bias and heterogeneity (p = 0.21, I(2) = 28.25). Similarly, in the carotids, there was a decrease in the CIMT, in millimeter, by -0.21 (95% CI -0.36 to -0.05) SMD and by -0.13 (95% CI -0.25 to -0.02) SMD, before and after accounting for publication bias and heterogeneity (p = 0.13, I(2) = 39.91; p = 0.54, I(2) = 0), respectively. In conclusion, these results suggest that intensive lifestyle modifications are associated with a decrease in coronary and carotid atherosclerotic burden.