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SOURCE CITATION: Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget stool RNA test for colorectal cancer screening. JAMA. 2023;330:1760-1768. 37870871.
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Adenoma , Neoplasias Colorretais , Humanos , Fezes , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Detecção Precoce de Câncer , Sangue Oculto , Adenoma/diagnóstico , Adenoma/genética , Programas de Rastreamento , ColonoscopiaRESUMO
BACKGROUND: We investigated associations between diabetes and mortality among participants with incident colorectal cancer (CRC) from the Southern Community Cohort Study. METHODS: Participants (73% non-Hispanic Black; 60% income < $15,000) were recruited between 2002-2009. Diabetes was self-reported at enrollment and follow-up surveys at approximately 5-year intervals. Incident CRC and mortality were identified via state registries and the National Death Index. Proportional hazards models calculated associations between diabetes with overall, CRC-specific mortality among 1059 participants with incident CRC. RESULTS: Diabetes prior to diagnosis is associated with elevated overall (hazard ratio [95% confidence interval]: (1.46[1.22-1.75]), and CRC-specific mortality (1.36[1.06-1.74])) after adjustment for tumor stage. For non-Hispanic Black and non-Hispanic White participants, consistent associations were observed for overall (1.35[1.10-1.66] vs. 1.89[1.31-2.72], respectively, p-interaction = 0.11) and CRC-specific mortality (1.30[0.99-1.71] vs. 1.77[1.06-2.95], respectively, p-interaction = 0.28). For individuals with incomes <$15,000/year, associations with overall (1.44[1.15-1.79]) and CRC-specific mortality (1.28[0.94-1.73]) were similar to the full sample. Associations with overall (1.71[1.37-2.13]) and CRC-specific mortality (1.65[1.22-2.22]) were highest for diabetes ≥ 10 years at diagnosis. CONCLUSIONS: Pre-diagnosis diabetes is associated with higher mortality among participants with incident CRC from a predominantly non-Hispanic Black cohort with lower socioeconomic status. The higher prevalence of diabetes in this population may contribute to racial disparities in CRC mortality.
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Studies of dietary inflammation potential and risks of colorectal cancer precursors are limited, particularly for sessile serrated lesions (SSLs). This study examines the association using the energy-adjusted dietary inflammatory index (E-DIITM), a measure of anti- and/or pro-inflammatory diet, in a large US colonoscopy-based case-control study of 3246 controls, 1530 adenoma cases, 472 hyperplastic polyp cases, and 180 SSL cases. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. Analyses were stratified by participant characteristics, and urinary prostaglandin E2 metabolite (PGE-M) and high-sensitivity plasma C-reactive protein (hs-CRP) levels, inflammation biomarkers. Highest E-DII™ intake was associated with significantly increased risks of colorectal adenomas (OR 1.36, 95% CI 1.11, 1.67), and hyperplastic polyps (OR 1.43, 95% CI 1.06, 1.98), compared with participants consuming the lowest E-DII™ quartile. A similar, but non-significant, increased risk was also observed for SSLs (OR 1.41, 95% CI 0.82, 2.41). The positive association was stronger in females (pinteraction <0.001), normal weight individuals (ptrend 0.01), and in individuals with lower inflammatory biomarkers (ptrend 0.02 and 0.01 for PGE-M and hs-CRP, respectively). A high E-DII™ is associated with colorectal polyp risk, therefore promoting an anti-inflammatory diet may aid in preventing colorectal polyps.
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Adenoma , Pólipos Adenomatosos , Pólipos do Colo , Neoplasias Colorretais , Neoplasias Retais , Feminino , Humanos , Pólipos do Colo/patologia , Estudos de Casos e Controles , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Adenoma/etiologia , Colonoscopia , Dieta/efeitos adversos , Inflamação , Biomarcadores , Fatores de RiscoRESUMO
SOURCE CITATION: Delgado-Lista J, Alcala-Diaz JF, Torres-Peña JD, et al. Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial. Lancet. 2022;399:1876-85. 35525255.
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Doenças Cardiovasculares , Dieta Mediterrânea , Doenças Cardiovasculares/prevenção & controle , Dieta com Restrição de Gorduras , Humanos , Prevenção SecundáriaRESUMO
INTRODUCTION: n-3 long-chain polyunsaturated fatty acids (LCPUFA) have anti-inflammatory effects and may reduce colorectal cancer risk. The purpose of this study was to evaluate the effects of n-3 LCPUFA supplementation on markers of rectal cell proliferation and apoptosis and examine how genetic variation in desaturase enzymes might modify this effect. METHODS: We conducted a randomized, double-blind, control six-month trial of 2.5 grams of n-3 LCPUFA per day compared to olive oil. Study participants had a history of colorectal adenomas. Randomization was stratified based on the gene variant rs174535 in the fatty acid desaturase 1 enzyme (FADS1). Our primary outcome was change in markers of rectal epithelial proliferation and apoptosis. RESULTS: A total of 141 subjects were randomized. We found no difference in apoptosis markers between participants randomized to n-3 LCPUFA compared to olive oil (P = 0.41). N-3 LCPUFA supplementation increased cell proliferation in the lower colonic crypt compared to olive oil (P = 0.03) however baseline indexes of proliferation were different between the groups at randomization. We found no evidence that genotype modified the effect. CONCLUSIONS: Our study did not show evidence of a proliferative or pro-apoptotic effect on n-3 LCPUFA supplementation on rectal mucosa regardless of the FADS genotype.ClinicalTrials.gov Identifier: NCT01661764Supplemental data for this article is available online at https://dx.doi.org/10.1080/01635581.2021.1955286.
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Neoplasias Colorretais , Ácidos Graxos Ômega-3 , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Dessaturase de Ácido Graxo Delta-5 , Suplementos Nutricionais , Ácidos Graxos , Ácidos Graxos Ômega-3/farmacologia , Humanos , Azeite de Oliva/farmacologiaRESUMO
BACKGROUND: Kidney reabsorption of magnesium (Mg) is essential for homeostasis. OBJECTIVES: We developed and validated models with the kidney reabsorption-related magnesium depletion score (MDS) to predict states of magnesium deficiency and disease outcomes. METHODS: MDS was validated in predicting body magnesium status among 77 adults (aged 62 ± 8 y, 51% men) at high risk of magnesium deficiency in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169) using the magnesium tolerance test (MTT). We then validated MDS for risk stratification and for associations with inflammation and mortality among >10,000 US adults (weighted: aged 48 ± 0.3 y, 47% men) in the NHANES, a nationally representative study. A proportional hazards regression model was used for associations between magnesium intake and the MDS with risks of total and cardiovascular disease (CVD) mortality. RESULTS: In the PPCCT, the area under the receiver operating characteristic (ROC) curve (AUC) for magnesium deficiency was 0.63 (95% CI: 0.50, 0.76) for the model incorporating the MDS with sex and age compared with 0.53 (95% CI: 0.40, 0.67) for the model with serum magnesium alone. In the NHANES, mean serum C-reactive protein significantly increased with increasing MDS (P-trend < 0.01) after adjusting for age and sex and other covariates, primarily among individuals with magnesium intake less than the Estimated Average Requirement (EAR; P-trend < 0.05). Further, we found that low magnesium intake was longitudinally associated with increased risks of total and CVD mortality only among those with magnesium deficiency predicted by MDS. MDS was associated with increased risks of total and CVD mortality in a dose-response manner only among those with magnesium intake less than the EAR. CONCLUSIONS: The MDS serves as a promising measure in identifying individuals with magnesium deficiency who may benefit from increased intake of magnesium to reduce risks of systemic inflammation and CVD mortality. This lays a foundation for precision-based nutritional interventions.
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Doenças Cardiovasculares , Magnésio , Idoso , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Modelos de Riscos ProporcionaisRESUMO
Diet modifies the risk of colorectal cancer (CRC), and inconclusive evidence suggests that yogurt may protect against CRC. We analysed the data collected from two separate colonoscopy-based case-control studies. The Tennessee Colorectal Polyp Study (TCPS) and Johns Hopkins Biofilm Study included 5446 and 1061 participants, respectively, diagnosed with hyperplastic polyp (HP), sessile serrated polyp, adenomatous polyp (AP) or without any polyps. Multinomial logistic regression models were used to derive OR and 95 % CI to evaluate comparisons between cases and polyp-free controls and case-case comparisons between different polyp types. We evaluated the association between frequency of yogurt intake and probiotic use with the diagnosis of colorectal polyps. In the TCPS, daily yogurt intake v. no/rare intake was associated with decreased odds of HP (OR 0·54; 95 % CI 0·31, 0·95) and weekly yogurt intake was associated with decreased odds of AP among women (OR 0·73; 95 % CI 0·55, 0·98). In the Biofilm Study, both weekly yogurt intake and probiotic use were associated with a non-significant reduction in odds of overall AP (OR 0·75; 95 % CI 0·54, 1·04) and (OR 0·72; 95 % CI 0·49, 1·06) in comparison with no use, respectively. In summary, yogurt intake may be associated with decreased odds of HP and AP and probiotic use may be associated with decreased odds of AP. Further prospective studies are needed to verify these associations.
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Pólipos do Colo/epidemiologia , Dieta , Iogurte , Pólipos Adenomatosos/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Probióticos/administração & dosagem , Fatores de Risco , Fatores Sexuais , Tennessee/epidemiologiaRESUMO
Animal studies have shown that polyunsaturated fatty acids (PUFAs) have antineoplastic and anti-inflammatory properties. Results from epidemiologic studies on specific types of PUFAs for lung cancer risk, however, are inconclusive. We prospectively evaluated the association of specific types of dietary PUFA intakes and lung cancer risk in two population-based cohort studies, the Shanghai Women's Health Study (SWHS) and Shanghai Men's Health Study (SMHS) with a total of 121,970 study participants (i.e., 65,076 women and 56,894 men). Dietary fatty acid intakes were derived from data collected at the baseline using validated food frequency questionnaires (FFQs). Cox proportional hazards model was performed to assess the association between PUFAs and lung cancer risk. Total, saturated and monounsaturated fatty acid intakes were not significantly associated with lung cancer risk. Total PUFAs intake was inversely associated with lung cancer risk [HRs and respective 95% CIs for quintiles 2-5 vs quintile 1: 0.84 (0.71-0.98), 0.97 (0.83-1.13), 0.86 (0.74-1.01) and 0.85 (0.73-1.00), ptrend = 0.11]. However, DHA intake was positively associated with lung cancer risk [HRs and 95% CIs: 1.01 (0.86-1.19), 1.20 (1.03-1.41), 1.21 (1.03-1.42) and 1.24 (1.05-1.47), ptrend = 0.001]. The ratio of n-6 PUFAs to n-3 PUFAs (i.e., 7:1) was inversely associated with lung cancer risk, particularly among never-smokers and adenocarcinoma patients. Total PUFAs and the ratio between n-6 PUFAs and n-3 PUFAs were inversely associated with lung cancer risk. This study highlights an important public health impact of PUFA intakes toward intervention/prevention programs of lung cancer.
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Dieta/efeitos adversos , Ácidos Graxos Insaturados/administração & dosagem , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Adulto , Idoso , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
PURPOSE: Several observational studies suggest that metformin reduces incidence cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes. METHODS: We constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. We used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors. We adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes. RESULTS: Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, we identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR] = 0.44, 95% CI 0.31, 0.64) compared to sulfonylurea. We found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use. CONCLUSIONS: In this large cohort study that accounted for time-related biases, we observed no association between the use of metformin and most cancers; however, we found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observations.
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Carcinoma Hepatocelular/prevenção & controle , Hipoglicemiantes/uso terapêutico , Neoplasias Hepáticas/prevenção & controle , Metformina/uso terapêutico , Idoso , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Compostos de Sulfonilureia/uso terapêutico , Estados Unidos/epidemiologia , VeteranosRESUMO
Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.
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Adenoma/sangue , Ácido Araquidônico/sangue , Neoplasias Colorretais/sangue , Ácido Eicosapentaenoico/sangue , Membrana Eritrocítica/metabolismo , Fosfolipídeos/química , Adenoma/etiologia , Adenoma/prevenção & controle , Biomarcadores/sangue , Estudos de Casos e Controles , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Dieta , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fosfolipídeos/sangue , Fatores de Risco , TennesseeRESUMO
BACKGROUND: Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk. METHODS: We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression. RESULTS: No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (ORALA=0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ⩾62 years for LA (ORLA=1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men <62 years (ORAA=1.05, 95%CI=1.02, 1.08; OREPA=1.04, 95%CI=1.01, 1.06; ORDPA=1.05, 95%CI=1.02, 1.08). CONCLUSION: Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer.
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Ácidos Graxos Insaturados/metabolismo , Neoplasias da Próstata/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Fatores de RiscoRESUMO
PURPOSE: Abnormalities in lipid levels have been associated with colorectal neoplasm risk; however, few studies have adjusted for use of cholesterol-lowering medications. The objective of this study was to determine the association of plasma lipid levels with adenoma risk while accounting for statin medication use. METHODS: We included 254 subjects with advanced adenoma, 246 with single small adenoma, 179 with multiple small adenoma cases, and 403 control participants in the Tennessee Colorectal Polyp Study who also had plasma lipid measurements performed. Data on the use of statin medications were available for 83.4% of these participants. The association between plasma lipids and adenoma risk was evaluated using logistic regression models. RESULTS: Participants in the highest quartile of HDL cholesterol (range 52-106 mg/dl) had an adjusted odds ratio of 0.49 (95% CI 0.23, 1.07), 0.35 (95% CI 0.13, 0.91), and 0.22 (95% CI 0.09, 0.54) for single small, multiple small, and advanced adenomas compared to the lowest quartile (range 12-34 mg/dl), respectively. Participants with the highest quartile of triglyceride levels (range 178-721 mg/dl) had an adjusted odds ratio of 2.40 (95% CI 1.26, 4.55), 1.67 (95% CI 0.66, 4.23), and 2.79 (95% CI 1.25, 6.23) for single small, multiple small, and advanced adenoma, respectively, compared to the lowest quartile (range 40-84 mg/dl). When restricted to individuals with known statin medication use, adjusting for statin use did not appreciably affect these results. CONCLUSION: We found a direct association between triglyceride plasma levels and an inverse association between plasma HDL cholesterol levels and adenoma risk. Both effects were not appreciably changed when accounting for the regular use of statin medication.
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Adenoma/sangue , HDL-Colesterol/sangue , Neoplasias Colorretais/sangue , Lipídeos/sangue , Adenoma/epidemiologia , Idoso , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tennessee/epidemiologiaRESUMO
IMPORTANCE: Preferred second-line medication for diabetes treatment after metformin failure remains uncertain. OBJECTIVE: To compare time to acute myocardial infarction (AMI), stroke, or death in a cohort of metformin initiators who added insulin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort constructed with national Veterans Health Administration, Medicare, and National Death Index databases. The study population comprised veterans initially treated with metformin from 2001 through 2008 who subsequently added either insulin or sulfonylurea. Propensity score matching on characteristics was performed, matching each participant who added insulin to 5 who added a sulfonylurea. Patients were followed through September 2011 for primary analyses or September 2009 for cause-of-death analyses. MAIN OUTCOMES AND MEASURES: Risk of a composite outcome of AMI, stroke hospitalization, or all-cause death was compared between therapies with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, cholesterol level, hemoglobin A1c level, creatinine level, blood pressure, body mass index, and comorbidities. RESULTS: Among 178,341 metformin monotherapy patients, 2948 added insulin and 39,990 added a sulfonylurea. Propensity score matching yielded 2436 metformin + insulin and 12,180 metformin + sulfonylurea patients. At intensification, patients had received metformin for a median of 14 months (IQR, 5-30), and hemoglobin A1c level was 8.1% (IQR, 7.2%-9.9%). Median follow-up after intensification was 14 months (IQR, 6-29 months). There were 172 vs 634 events for the primary outcome among patients who added insulin vs sulfonylureas, respectively (42.7 vs 32.8 events per 1000 person-years; adjusted hazard ratio [aHR], 1.30; 95% CI, 1.07-1.58; P = .009). Acute myocardial infarction and stroke rates were statistically similar, 41 vs 229 events (10.2 and 11.9 events per 1000 person-years; aHR, 0.88; 95% CI, 0.59-1.30; P = .52), whereas all-cause death rates were 137 vs 444 events, respectively (33.7 and 22.7 events per 1000 person-years; aHR, 1.44; 95% CI, 1.15-1.79; P = .001). There were 54 vs 258 secondary outcomes: AMI, stroke hospitalizations, or cardiovascular deaths (22.8 vs 22.5 events per 1000 person-years; aHR, 0.98; 95% CI, 0.71-1.34; P = .87). CONCLUSIONS AND RELEVANCE: Among patients with diabetes who were receiving metformin, the addition of insulin vs a sulfonylurea was associated with an increased risk of a composite of nonfatal cardiovascular outcomes and all-cause mortality. These findings require further investigation to understand risks associated with insulin use in these patients.
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Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/administração & dosagem , Adulto , Idoso , Complicações do Diabetes/mortalidade , Diabetes Mellitus/mortalidade , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/administração & dosagem , Incidência , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Estudos Retrospectivos , Risco , Acidente Vascular Cerebral/mortalidade , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos , Falha de TratamentoRESUMO
BACKGROUND: Metformin, utilized to manage hyperglycemia, has been linked to a reduced risk of colorectal cancer (CRC) among individuals with diabetes. However, evidence is lacking for non-Hispanic Black individuals and those with lower socioeconomic status (SES), who face elevated risk for both diabetes and CRC. In this study, we investigated the association between metformin use and incident CRC risk within the Southern Community Cohort Study (SCCS), a racially- and SES-diverse prospective cohort. METHODS: Participants reported their diabetes diagnosis and medications, including metformin, upon enrollment (2002-2009) and during follow-up surveys approximately every five years. Incident cases of CRC were identified through state cancer registries and the National Death Index. Proportional hazards models were employed to explore the relationship between metformin use and CRC risk, adjusted for cancer risk factors. RESULTS: A total of 25,992 participants with diabetes were included in the analysis, among whom 10,095 were taking metformin. Of these participants, 76% identified as non-Hispanic Black, and 60% reported household incomes <$15,000/year. Metformin use was associated with a significantly lower CRC risk (HR [95% CI]: 0.71 [0.55-0.93]), with consistent results for both colon (0.80 [0.59-1.07]) and rectal cancers (0.49 [0.28-0.86]). The protective association appeared to be stronger among non-Hispanic White individuals (0.51 [0.31-0.85]) compared to non-Hispanic Black participants (0.80 [0.59-1.08], p-interaction =.13). Additionally, a protective association was observed among obese individuals (BMI ≥30â¯kg/m2, 0.59 [0.43-0.82] but not among non-obese participants (0.99 [0.65-1.51], p-interaction =.05) CONCLUSION: Our findings indicate that metformin use is associated with a reduced risk of CRC in individuals with diabetes, including among those from predominantly low SES backgrounds. These results support previous epidemiological findings, and demonstrate that the protective association for metformin in relation to incident CRC likely generalizes to populations with higher underlying risk.
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Neoplasias Colorretais , Hipoglicemiantes , Metformina , Humanos , Metformina/uso terapêutico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Masculino , Feminino , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Estudos Prospectivos , Idoso , Fatores de Risco , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Incidência , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , AdultoRESUMO
UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the ß-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F2-IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F2t-IsoP and 5-epi-5-F2t-IsoP, two abundantly produced F2-IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F2-IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F2t-IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F2t-IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F2-IsoPs in human urine and showed that F2-IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F2-IsoP levels can be modified by factors other than redox mechanisms.
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F2-Isoprostanos , Isoprostanos , Humanos , Glucuronídeos , Estresse Oxidativo , Eicosanoides , Difosfato de UridinaRESUMO
INTRODUCTION: There are many myths regarding Alzheimer's disease (AD) that have been circulated on the internet, each exhibiting varying degrees of accuracy, inaccuracy, and misinformation. Large language models, such as ChatGPT, may be a valuable tool to help assess these myths for veracity and inaccuracy; however, they can induce misinformation as well. OBJECTIVE: This study assesses ChatGPT's ability to identify and address AD myths with reliable information. METHODS: We conducted a cross-sectional study of attending geriatric medicine clinicians' evaluation of ChatGPT (GPT 4.0) responses to 16 selected AD myths. We prompted ChatGPT to express its opinion on each myth and implemented a survey using REDCap to determine the degree to which clinicians agreed with the accuracy of each of ChatGPT's explanations. We also collected their explanations of any disagreements with ChatGPT's responses. We used a 5-category Likert-type scale with a score ranging from -2 to 2 to quantify clinicians' agreement in each aspect of the evaluation. RESULTS: The clinicians (n = 10) were generally satisfied with ChatGPT's explanations. Among the 16 myths, the clinicians were generally satisfied with these explanations, with [mean (SD) score of 1.1(±0.3)]. Most clinicians selected "Agree" or "Strongly Agree" for each statement. Some statements obtained a small number of "Disagree" responses. There were no "Strongly Disagree" responses. CONCLUSION: Most surveyed health care professionals acknowledged the potential value of ChatGPT in mitigating AD misinformation; however, the need for more refined and detailed explanations of the disease's mechanisms and treatments was highlighted.
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BACKGROUND: The aim of this study was to build electronic algorithms using a combination of structured data and natural language processing (NLP) of text notes for potential safety surveillance of 9 postoperative complications. METHODS: Postoperative complications from 6 medical centers in the Southeastern United States were obtained from the Veterans Affairs Surgical Quality Improvement Program (VASQIP) registry. Development and test datasets were constructed using stratification by facility and date of procedure for patients with and without complications. Algorithms were developed from VASQIP outcome definitions using NLP-coded concepts, regular expressions, and structured data. The VASQIP nurse reviewer served as the reference standard for evaluating sensitivity and specificity. The algorithms were designed in the development and evaluated in the test dataset. RESULTS: Sensitivity and specificity in the test set were 85% and 92% for acute renal failure, 80% and 93% for sepsis, 56% and 94% for deep vein thrombosis, 80% and 97% for pulmonary embolism, 88% and 89% for acute myocardial infarction, 88% and 92% for cardiac arrest, 80% and 90% for pneumonia, 95% and 80% for urinary tract infection, and 77% and 63% for wound infection, respectively. A third of the complications occurred outside of the hospital setting. CONCLUSIONS: Computer algorithms on data extracted from the electronic health record produced respectable sensitivity and specificity across a large sample of patients seen in 6 different medical centers. This study demonstrates the utility of combining NLP with structured data for mining the information contained within the electronic health record.
Assuntos
Algoritmos , Registros Eletrônicos de Saúde , Complicações Pós-Operatórias/epidemiologia , Injúria Renal Aguda/epidemiologia , Parada Cardíaca/epidemiologia , Humanos , Infarto do Miocárdio/epidemiologia , Processamento de Linguagem Natural , Pneumonia/epidemiologia , Vigilância da População , Embolia Pulmonar/epidemiologia , Sepse/epidemiologia , Estados Unidos/epidemiologia , Infecções Urinárias/epidemiologia , Trombose Venosa/epidemiologia , Infecção dos Ferimentos/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVE: We recently reported that kidney function declined faster among initiators of sulfonylureas compared to metformin; however, sulfonylurea use compared to metformin use was also associated with increases in body mass index (BMI) and systolic blood pressure (SBP). We sought to determine if differences between sulfonylureas and metformin on kidney function decline were mediated by differential effects on BMI, SBP, or glucose control. METHODS: We identified 13,238 veterans who initiated sulfonylurea or metformin treatment (20002007) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/minute, and followed them until a study event occurred, non-persistence on treatment, loss of follow-up, or end of the study. The composite outcome was a sustained decline from baseline eGFR of ≥25%, end-stage renal disease, or death. We estimated the association of cumulative measurements of potential mediators including BMI, SBP, and glycated hemoglobin on the study outcome. We determined if controlling for these time-varying covariates accounted for the differences in outcome between sulfonylurea and metformin initiators. RESULTS: Compared to sulfonylurea use, metformin use was associated with a lower risk for renal function decline or death [adjusted hazard ratio (aHR) 0.82, 95% confidence interval 0.70, 0.97]. This protective association remained significant [aHR 0.83 (0.700.98)] when accounting for the cumulative time-varying measurements of the three mediators of interest. CONCLUSION: Metformin initiation was associated with a lower risk of kidney function decline or death compared to sulfonylureas, which which appeared to be independent of changes in BMI, SBP, and glycated hemoglobin over time.