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抗菌药物暴露对帕金森病风险的影响。

Effects of antimicrobial exposure on the risk of Parkinson's disease.

作者信息

Pal Gian, Bennett Laura, Roy Jason, Nyandege Abner, Mouradian M Maral, Gerhard Tobias, Horton Daniel B

机构信息

Department of Neurology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA.

出版信息

Parkinsonism Relat Disord. 2024 Oct;127:107081. doi: 10.1016/j.parkreldis.2024.107081. Epub 2024 Jul 30.

Abstract

BACKGROUND

We aimed to assess how antimicrobial exposure affects Parkinson's disease (PD) risk.

METHODS

A nested case-control study was performed to examine the association between antimicrobial exposure and newly diagnosed PD using the Clinical Practice Research Datalink (CPRD). Each PD case was matched by age, sex, and year of diagnosis (index date) to up to 15 controls. Number of prescribed antimicrobial courses was assessed 1-5, 6-10, and 11-15 years prior to the index date. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and false discovery rate-adjusted p-values between antimicrobial exposure and risk of PD.

RESULTS

We compared 12,557 PD cases with 80,804 matched controls. We found an inverse dose-response relationship between number of penicillin courses and PD risk across multiple time periods (5+ courses, 1-5 years prior: OR 0.85, 95 % CI 0.76-0.95, p = 0.043; 6-10 years prior: OR 0.84, 95 % CI: 0.73-0.95, p = 0.059; 11-15 years prior: OR 0.87, 95 % CI 0.74-1.02, p = 0.291). The number of macrolide courses was inversely but not significantly associated with PD risk 1-5 years prior to the index date (OR 0.89-0.91, 95 % CI: 0.79-0.99, adjusted p = 0.140-0.167). Exposure to ≥2 courses of antifungals 1-5 years prior was associated with an increased risk of PD (OR 1.16, 95 % CI: 1.06-1.27, p = 0.020).

CONCLUSIONS

In a large UK-representative population, the risk of PD was modestly lower among adults who had previously received multiple courses of penicillins in the last 15 years and modestly higher among those exposed to antifungal medicines in recent years.

摘要

背景

我们旨在评估抗菌药物暴露如何影响帕金森病(PD)风险。

方法

进行了一项巢式病例对照研究,使用临床实践研究数据链(CPRD)来检验抗菌药物暴露与新诊断的PD之间的关联。每个PD病例按年龄、性别和诊断年份(索引日期)与多达15名对照进行匹配。在索引日期前1 - 5年、6 - 10年和11 - 15年评估开具的抗菌药物疗程数。使用带有广义估计方程(GEE)的逻辑回归来估计抗菌药物暴露与PD风险之间的比值比(OR)和错误发现率调整后的p值。

结果

我们将12,557例PD病例与80,804名匹配对照进行了比较。我们发现在多个时间段内,青霉素疗程数与PD风险之间存在剂量反应负相关关系(5个及以上疗程,索引日期前1 - 5年:OR 0.85,95% CI 0.76 - 0.95,p = 0.043;索引日期前6 - 10年:OR 0.84,95% CI:0.73 - 0.95,p = 0.059;索引日期前11 - 15年:OR 0.87,95% CI 0.74 - 1.02,p = 0.291)。在索引日期前1 - 5年,大环内酯类药物疗程数与PD风险呈负相关,但无显著关联(OR 0.89 - 0.91,95% CI:0.79 - 0.99,调整后p = 0.140 - 0.167)。在索引日期前1 - 5年暴露于≥2个抗真菌药物疗程与PD风险增加相关(OR 1.16,95% CI:1.06 - 1.27,p = 0.020)。

结论

在具有英国代表性的大量人群中,在过去15年中曾接受多个青霉素疗程的成年人中,PD风险略低,而近年来接触抗真菌药物的人群中PD风险略高。

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