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阿片类镇痛药的使用与侵袭性肺炎球菌病风险:一项巢式病例对照研究。

Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case-Control Study.

机构信息

Vanderbilt University Medical Center, Nashville, Tennessee (A.D.W., W.S., C.M.S., E.F.M.).

Vanderbilt University Medical Center and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee (M.R.G., C.G.G.).

出版信息

Ann Intern Med. 2018 Mar 20;168(6):396-404. doi: 10.7326/M17-1907. Epub 2018 Feb 13.

Abstract

BACKGROUND

Although certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown.

OBJECTIVE

To test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD).

DESIGN

Nested case-control study.

SETTING

Tennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014).

PATIENTS

1233 case patients with IPD aged 5 years and older matched to 24 399 control participants by diagnosis date, age, and county of residence.

MEASUREMENTS

Opioid use was measured on the basis of pharmacy prescription fills. Invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site. The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and nonpneumonia IPD cases separately.

RESULTS

Persons in the case group had greater odds than control participants of being current opioid users (adjusted odds ratio [aOR], 1.62 [95% CI, 1.36 to 1.92]). Associations were strongest for opioids that were long acting (aOR, 1.87 [CI, 1.24 to 2.82]), of high potency (aOR, 1.72 [CI, 1.32 to 2.25]), or were used at high dosages (50 to 90 morphine milligram equivalents [MME]/d: aOR, 1.71 [CI, 1.22 to 2.39]; ≥90 MME/d: aOR, 1.75 [CI, 1.33 to 2.29]). Results were consistent when the IPD risk score was taken into account and pneumonia and nonpneumonia IPD were analyzed separately.

LIMITATIONS

Unmeasured confounding and measurement error, although sensitivity analyses suggested that neither was likely to affect results. Actual opioid use and other nonprescription use (such as illicit opioid use) were not measured.

CONCLUSION

Opioid use is associated with an increased risk for IPD and represents a novel risk factor for these diseases.

PRIMARY FUNDING SOURCE

National Institutes of Health.

摘要

背景

虽然某些阿片类镇痛药具有免疫抑制作用,并会增加动物感染的风险,但处方类阿片类药物的使用对人类感染风险的临床影响尚不清楚。

目的

检验以下假设,即处方类阿片类药物的使用是侵袭性肺炎球菌病(IPD)的一个独立风险因素。

设计

巢式病例对照研究。

设置

田纳西州医疗补助数据库与医疗保险和活性细菌核心监测系统数据库相链接(1995 年至 2014 年)。

患者

1233 例年龄在 5 岁及以上的 IPD 病例患者与 24399 例按诊断日期、年龄和居住县匹配的对照参与者。

测量方法

根据药房处方记录来衡量阿片类药物的使用情况。通过从无菌部位分离肺炎链球菌来确定侵袭性肺炎球菌病。病例组与对照组之间比较当前阿片类药物使用的可能性,同时考虑已知的 IPD 风险因素。二级分析根据阿片类药物特征对阿片类药物使用情况进行分类,应用 IPD 风险评分确保暴露组之间的可比性,并分别分析肺炎和非肺炎 IPD 病例。

结果

与对照组参与者相比,病例组参与者为当前阿片类药物使用者的可能性更大(调整后的优势比[OR],1.62 [95%CI,1.36 至 1.92])。与长效(OR,1.87 [CI,1.24 至 2.82])、高效(OR,1.72 [CI,1.32 至 2.25])或高剂量(50 至 90 吗啡毫克当量[MME]/d:OR,1.71 [CI,1.22 至 2.39];≥90 MME/d:OR,1.75 [CI,1.33 至 2.29])的阿片类药物使用的关联最强。当考虑到 IPD 风险评分以及分别分析肺炎和非肺炎 IPD 时,结果仍然一致。

局限性

未测量的混杂因素和测量误差,尽管敏感性分析表明这两者都不太可能影响结果。未测量实际阿片类药物的使用情况和其他非处方使用(如非法阿片类药物的使用)。

结论

阿片类药物的使用与 IPD 风险增加有关,代表了这些疾病的一个新的风险因素。

主要资金来源

美国国立卫生研究院。

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