The Association between the Risk of Aortic Aneurysm/Aortic Dissection and the Use of Fluroquinolones: A Systematic Review and Meta-Analysis.
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SUBMITTER: Lai CC
PROVIDER: S-EPMC8230555 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Previous studies have drawn causal associations between fluoroquinolone use and collagen pathologies including tendon rupture and retinopathy. This meta-analysisattempted to assess the association between fluoroquinolone use and the risk of aortic dissection or aortic aneurysm. A systematic search was performed on Medline, EMBASE, and the Cochrane library. 9 studies were included in final analysis. Primary random-effects meta-analysis of 7 studies, excluding 2 pharmacovigilance studies demonstrated statistically increased odds of aortic dissection (OR, 2.38; 95% CI, 1.71-3.32) aortic aneurysm (OR, 1.98; 95% CI, 1.59-2.48), and aortic aneurysm or dissection (OR, 1.47; 95% CI, 1.13-1.89; I2 = 72%) with current use of fluoroquinolones compared to their nonuser counterparts. Based on the "number needed-to-harm" analysis, 7246 (95% CI: 4329 to 14,085) patients would need to be treated with fluoroquinolones for a duration of at least three days in order for one additional patient to be harmed, assuming a population baseline incidence of aortic dissection and aneurysm rupture to be 10 per 100,000 patient-years. With strong statistical association, these findings suggest a causal relationship, warranting future research to elucidate the pathophysiological and mechanistic plausibility of this association. These findings however, should not cease prescription of fluoroquinolones, especially when clinically indicated.
| S-EPMC8154986 | biostudies-literature
Project description:ImportancePrior observational studies have suggested that fluoroquinolone use may be associated with more than 2-fold increased risk of aortic aneurysm or aortic dissection (AA/AD). These studies, however, did not fully consider the role of coexisting infections and the risk of fluoroquinolones relative to other antibiotics.ObjectiveTo estimate the risk of AA/AD associated with infections and to assess the comparative risk of AA/AD associated with fluoroquinolones vs other antibiotics with similar indication profiles among patients with the same types of infections.Designs, settings, and participantsThis nested case-control study identified 21 651 176 adult patients from a nationwide population-based health insurance claims database from January 1, 2009, to November 30, 2015. Each incident case of AA/AD was matched with 10 control individuals by age, sex, and follow-up duration in the database using risk-set sampling. Analysis of the data was conducted from April 2019 to March 2020.ExposuresInfections and antibiotic use within a 60-day risk window before the occurrence of AA/AD.Main outcomes and measuresConditional logistic regression was used to estimate the odds ratios (ORs) and 95% CIs comparing infections for which fluoroquinolones are commonly used with no infection within a 60-day risk window before outcome occurrence, adjusting for baseline confounders and concomitant antibiotic use. The adjusted ORs comparing fluoroquinolones with antibiotics with similar indication profiles within patients with indicated infections were also estimated.ResultsA total of 28 948 cases and 289 480 matched controls were included (71.37% male; mean [SD] age, 67.41 [15.03] years). Among these, the adjusted OR of AA/AD for any indicated infections was 1.73 (95% CI, 1.66-1.81). Septicemia (OR, 3.16; 95% CI, 2.63-3.78) and intra-abdominal infection (OR, 2.99; 95% CI, 2.45-3.65) had the highest increased risk. Fluoroquinolones were not associated with an increased AA/AD risk when compared with combined amoxicillin-clavulanate or combined ampicillin-sulbactam (OR, 1.01; 95% CI, 0.82-1.24) or with extended-spectrum cephalosporins (OR, 0.88; 95% CI, 0.70-1.11) among patients with indicated infections. The null findings for fluoroquinolone use remained robust in different subgroup and sensitivity analyses.Conclusions and relevanceThese results highlight the importance of accounting for coexisting infections while examining the safety of antibiotics using real-world data; the findings suggest that concerns about AA/AD risk should not deter fluoroquinolone use for patients with indicated infections.
| S-EPMC7489369 | biostudies-literature
Project description:ImportancePrevious observational studies have suggested that fluoroquinolones are associated with aortic aneurysm or dissection, but these studies may be subject to confounding by indication or surveillance bias.ObjectiveTo assess the association of fluoroquinolones with risk of aortic aneurysm or aortic dissection (AA/AD) while accounting for potential confounding by fluoroquinolone indication and bias owing to differential surveillance.Design, setting, and participantsIn an observational cohort study using a US commercial claims database, 2 pairwise 1:1 propensity score-matched cohorts were identified: patients aged 50 years or older with a diagnosis of pneumonia 3 days or less before initiating treatment with a fluoroquinolone or azithromycin and patients aged 50 years or older with a urinary tract infection (UTI) diagnosis 3 days or less before initiating a fluoroquinolone or combined trimethoprim and sulfamethoxazole. Hazard ratios (HRs) and 95% CIs were estimated controlling for 85 baseline confounders. In a secondary analysis, patients receiving fluoroquinolones were compared with those receiving amoxicillin, both with and without considering baseline aortic imaging, to address differences in detection of AA/AD before antibiotic use. Data on patients within the database from January 1, 2003, through September 30, 2015, were analyzed. Data analysis was conducted from July 23, 2019, to July 6, 2020.Main outcomes and measuresHospitalization for AA/AD occurring within 60 days following treatment initiation.ResultsAfter propensity score matching, patient characteristics were well balanced, with 279 554 patients (mean [SD] age, 63.66 [10.93] years; 149 976 women [53.6%]) in the pneumonia cohort and 948 364 patients (mean [SD] age, 62.06 [10.33] years; 823 667 women [86.9%]) in the UTI cohort. Initiators of fluoroquinolones (n = 139 772 pairs in the pneumonia cohort and n = 474 182 pairs in the UTI cohort) had an increased rate of AA/AD compared with initiators of azithromycin (HR, 2.57; 95% CI, 1.36-4.86; incidence, 0.03% for fluoroquinolones vs 0.01% for azithromycin) but no increased rate compared with initiators of combined trimethoprim and sulfamethoxazole (HR, 0.99; 95% CI, 0.62-1.57; incidence, <0.01% in both UTI groups). Secondary analysis using amoxicillin as a comparator (n = 3 976 162 pairs) produced results consistent with those from earlier studies (HR, 1.54; 95% CI, 1.33-1.79; incidence, <0.01% in both groups). Requiring baseline imaging in this cohort (n = 542 649 pairs) to address surveillance bias attenuated the increased rate (HR, 1.13; 95% CI, 0.96-1.33; incidence, 0.06% for fluoroquinolones vs 0.05% for amoxicillin).Conclusions and relevanceThe findings of this nationwide cohort study of adults with pneumonia or UTI suggest an increased relative rate of AA/AD associated with fluoroquinolones within the pneumonia cohort but not within the UTI cohort. In both cohorts, the absolute rate of AA/AD appeared to be low (<0.1%). The increased relative rate observed in the pneumonia cohort may be due to residual confounding or surveillance bias.
| S-EPMC7489402 | biostudies-literature
Project description:ObjectiveThe aim of this study was to determine the association between fluoroquinolones (FQs) use, the risk of de novo aortic aneurysm or dissection (AAD), and the prognosis of patients with pre-existing AAD.Materials and methodsWe searched PubMed, EMBASE, CENTRAL, Scopus, and Web of Science on 31 March 2022. Observational studies that evaluated the association of FQs with AAD risk in the general population or FQs with the prognosis of patients with preexisting AAD and presented adjusted effect estimates were included. Two reviewers assessed study eligibility, extracted data, and assessed the risk of bias and certainty of evidence using GRADE.ResultsOf the 13 included studies, 11 focused on the association of FQs with de novo AAD incidence, and only one study investigated the association of FQs with the patient with AAD prognosis. FQ use was associated with an increased risk of de novo AAD within 30 days (RR: 1.42; 95% CI: 1.11-1.81; very low certainty) and 60 days (RR: 1.44; 95% CI: 1.26-1.64; low certainty). Specifically, the association was significant when compared with amoxicillin, azithromycin, doxycycline, or no antibiotic use. Furthermore, patients with preexisting AAD exposure to FQ had an increased risk of all-cause mortality (RR: 1.61; 95% CI: 1.50-1.73; moderate certainty) and aortic-specific mortality (RR: 1.80; 95% CI: 1.50-2.15; moderate certainty), compared to the non-exposed FQ group within a 60-day risk period.ConclusionFQs were associated with an increased incidence of AAD in the general population and a higher risk of adverse outcomes in patients with preexisting AAD. Nevertheless, the results may be affected by unmeasured confounding factors. This should be considered by physicians contemplating using FQs in patients with aortic dilation and those at high risk of AAD.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021230171].
| S-EPMC9396038 | biostudies-literature
Project description:To investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection.Nationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection.Sweden, July 2006 to December 2013.360?088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360?088).Cox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment.Within the 60 day risk period, the rate of aortic aneurysm or dissection was 1.2 cases per 1000 person years among fluoroquinolone users and 0.7 cases per 1000 person years among amoxicillin users. Fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection (hazard ratio 1.66 (95% confidence interval 1.12 to 2.46)), with an estimated absolute difference of 82 (95% confidence interval 15 to 181) cases of aortic aneurysm or dissection by 60 days per 1 million treatment episodes. In a secondary analysis, the hazard ratio for the association with fluoroquinolone use was 1.90 (1.22 to 2.96) for aortic aneurysm and 0.93 (0.38 to 2.29) for aortic dissection.In a propensity score matched cohort, fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection. This association appeared to be largely driven by aortic aneurysm.
| S-EPMC5842359 | biostudies-literature
Project description:Background Fluoroquinolones are first-line antibiotics recommended for the treatment of complicated urinary tract infections (UTIs), with frequent reports of adverse effects of aortic aneurysm (AA) and aortic dissection (AD). We examined whether fluoroquinolones can increase the risk of AA and AD in patients with UTIs in the Taiwanese population. Methods and Results We used the National Health Insurance Research Database to identify patients diagnosed with UTIs under single antibiotic treatment of fluoroquinolones and first-, second-, or third-generation cephalosporins. An AA and AD diagnosis within a year constituted the study event. Multivariable analysis with a multiple Cox regression model was applied for comparing the hazard risk of AA and AD between fluoroquinolones and first- or second-generation cephalosporins. Propensity score matching was performed to reduce the potential for bias caused by measured confounding variables. Among 1 249 944 selected patients with UTIs, 28 568 patients were assigned to each antibiotic group after propensity score matching. The incidence of AA and AD was not significantly different between the fluoroquinolones and first- or second-generation cephalosporins (adjusted HR [aHR], 0.86 [95% CI, 0.59-1.27]). However, the mortality increased in the fluoroquinolones group (aHR, 1.10 [95% CI, 1.04-1.16]). Conclusions Compared with first- or second-generation cephalosporins, fluoroquinolones were not associated with increased risk of AA and AD in patients with UTI. However, a significant risk of mortality was still found in patients treated with fluoroquinolones. The priority is to control infections with adequate antibiotics rather than exclude fluoroquinolones considering the risk of AA and AD for patients with UTI.
| S-EPMC9075302 | biostudies-literature
Project description:ImportanceThe natural history of ascending aortic aneurysm (AsAA) is currently not well characterized.ObjectiveTo summarize and analyze existing literature on the natural history of AsAA.Data sourcesA search of Ovid MEDLINE (January 1, 1946, to May 31, 2017) and Embase (January 1, 1974, to May 31, 2017) was conducted.Study selectionStudies including patients with AsAA were considered for inclusion; studies were excluded if they considered AsAA, arch, and descending thoracic aneurysm as 1 entity or only included descending aneurysms, patients with heritable or genetic-related aneurysms, patients with replaced bicuspid aortic valves, patients with acute aortic syndrome, or those with mean age less than 16 years. Two independent reviewers identified 20 studies from 7198 unique studies screened.Data extraction and synthesisData extraction was performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline; 2 reviewers independently extracted the relevant data. Summary effect measures of the primary outcomes were obtained by logarithmically pooling the data with an inverse variance-weighted random-effects model. Metaregression was performed to assess the relationship between initial aneurysm size, etiology, and the primary outcomes.Main outcomes and measuresThe primary composite outcome was incidence of all-cause mortality, aortic dissection, and aortic rupture. Secondary outcomes were growth rate, incidence of proximal aortic dissection or rupture, elective ascending aortic repair, and all-cause mortality.ResultsTwenty studies consisting of 8800 patients (mean [SD] age, 57.75 [9.47] years; 6653 [75.6%] male) with a total follow-up time of 31 823 patient-years were included. The mean AsAA size at enrollment was 42.6 mm (range, 35.5-56.0 mm). The combined effect estimate of annual aneurysm growth rate was 0.61 mm/y (95% CI, 0.23-0.99 mm/y). The pooled incidence of elective aortic surgery was 13.82% (95% CI, 6.45%-21.41%) over a median (interquartile range) follow-up of 4.2 (2.9-15.0) years. The linearized mortality rate was 1.99% per patient-year (95% CI, 0.83%-3.15% per patient-year), and the linearized rate of the composite outcome of all-cause mortality, aortic dissection, and aortic rupture was 2.16% per patient-year (95% CI, 0.79%-3.55% per patient year). There was no significant relationship between year of study completion and the initial aneurysm size and primary outcomes.Conclusions and relevanceThe growth rate of AsAA is slow and has implications for the interval of imaging follow-up. The data on the risk of dissection, rupture, and death of ascending aortic aneurysm are limited. A randomized clinical trial may be required to understand the benefit of surgical intervention compared with surveillance for patients with moderately dilated ascending aorta.
| S-EPMC6324275 | biostudies-literature
Project description: Not available
| S-EPMC8302985 | biostudies-literature
Project description:ImportanceMarijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the association of marijuana use with the development of cancer is not clear.ObjectiveTo assess the association of marijuana use with cancer development.Data sourcesA search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019.Study selectionEnglish-language studies involving adult marijuana users and reporting cancer development. The search strategy contained the following 2 concepts linked together with the AND operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND cancer OR malignancy OR carcinoma OR tumor OR neoplasm.Data extraction and synthesisTwo reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence strength by consensus.Main outcomes and measuresRates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Meta-analysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneity was low to moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95% CIs.ResultsTwenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuana was not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95% CI, 1.03-1.81; P = .03; I2 = 0%) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10-3.11; P = .04; I2 = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes.Conclusions and relevanceLow-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding of marijuana's association with lung, oral, and other cancers.Trial registrationPROSPERO identifier: CRD42018102457.
| S-EPMC6902836 | biostudies-literature
Project description:BackgroundRecent studies have raised concern about the association of fluoroquinolones with an increased risk of aortic aneurysm and aortic dissection. We aimed to evaluate such risk in a Korean population.MethodsWe conducted a nested case-control study using data from the National Health Insurance Service collected from 2013 to 2017 in Korea. The study cohort included patients older than 40 years and excluded patients who had used fluoroquinolones or been diagnosed with aortic aneurysm, aortic dissection, or related diseases 1 year prior to the cohort entry date. We randomly matched four controls in the risk set with each case of aortic aneurysm and aortic dissection (same sex, age, and cohort entry date). We assessed the risk of aortic aneurysm and aortic dissection from fluoroquinolones and adjusted for potential confounders using a conditional logistic regression model.ResultsA total of 29,638 aortic aneurysm and aortic dissection patients were identified between 2014 and 2017. The use of fluoroquinolones within a year was associated with a 10% increased risk of aortic aneurysm and aortic dissection (adjusted odds ratio: 1.10, 95% CI 1.07-1.14, p < 0.05) compared with nonusers. The risk was higher in patients who had used fluoroquinolones within 60 days (adjusted odds ratio: 1.53, 95% CI 1.46-1.62, p < 0.05). The risk of aortic aneurysm and aortic dissection positively correlated with the cumulative dose and duration of fluoroquinolone therapy (p < 0.001).ConclusionsOur study provides real-world evidence of the risk of aortic aneurysm and aortic dissection from fluoroquinolones in Korea. Patients and medical professionals should be aware that fluoroquinolones can increase the risk of aortic aneurysm and aortic dissection, which may be acerbated by high dosage and duration of use.
| S-EPMC8842902 | biostudies-literature