結核病以及癌症之初級，次級以及三級預防

Primary, secondary and tertiary prevention of tuberculosis and malignancy

李孟叡(Meng-Rui Lee)

指導教授 ： 陳建煒

共同指導教授 ： 林先和(Hsien-Ho Lin)

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2019年)

https://doi.org/10.6342/NTU201900918

摘要

背景介紹
結核病以及癌症乃是兩個全球相當重要之傳染性以及非傳染性疾病，在公衛的領域中，針對這兩個疾病的預防醫學，是相當重要的課題，因此，我們針對這兩個全球性的重要疾病，在初級，次級以及三級預防中，探討關鍵的課題以及研究。
方法與程序
在初級預防中，我們探討糖尿病是否會增加潛伏結核感染的風險，在過去的研究中，主要是發現糖尿病會增加活動性結核的風險以及影響預後，對於潛伏結核感染這一塊，少有著墨，而我們將利用統合分析的方式，來研究糖尿病是否會增加結核潛伏感染的風險。
在次級預防中，我們探討一個新的氟喹諾酮(fluoroquinolone)，gemifloxacin，是否會造成結核診斷延誤，過去認為針對結核病患者使用對於結核菌有效之氟喹諾酮類抗生素，會造成結核病患者症狀改善，而造成診斷延誤，而新一代的氟喹諾酮gemifloxacin，因為其對於結核菌無抗菌力，是否就因此而比較不會造成結核病診斷延誤，則尚未有定論。在這研究中，我們將使用北台灣多中心三家醫院的患者資料以及臺灣的健保資料庫，進行世代研究。
在三級預防中，我們分析，是否入住加護病房，對於發生敗血性休克的第四期癌症患者的長期預後是否有幫助。過去認為，因為第四期癌症患者普遍預後極差，因此當產生重症疾患如敗血性休克時，入住加護病房接受積極治療，將只是帶來患者痛苦而對於整體預後幫助不大，但是隨著癌症以及重症醫療的進步，此一觀念是否需要改變則尚屬未知，本研究則將利用臺灣癌症登記檔以及臺灣健保資料庫進行串聯分析。
結果
在初級預防議題中，我們統合了十三個研究，收入了七個國家，38263受試者，發現糖尿病跟潛伏結核感染有統計上顯著的相關性，但是其強度並沒有一般認為的高(OR:1.18(95% CI:1.06-1.30))。
在次級預防議題中，藉由收入了醫院世代201位患者以及健保資料庫世代中3544位患者，我們發現在經由傾向分數(propensity score)配對後，使用gemifloxacin的患者並沒有較短的結核病診斷延誤。
在三級預防中，我們共收入了11825位第四期癌症併敗血性休克的患者，其中有6089位患者有入住加護病房，整體院內死亡率約七成，經由傾向分數配對後，我們發現入住加護病房的患者有較佳的整體存活HR: 0.76, 95% CI: 0.72-0.79)，較低的院內死亡率(OR: 0.61, 95% CI: 0.55-0.68)，以及較佳的出院後存活(HR: 0.77, 95% CI: 0.70-0.85)。
討論與結論
根基於我們的研究，我們確立了糖尿病會增加潛伏結核感染的風險，但由於風險比並不如想像的高，要特地針對糖尿病進行潛伏結核感染篩檢仍需有更全盤的考慮。而對於結核病的診斷的部分，高的臨床警覺性加上積極進行相關結核菌學檢查依然是縮短診斷延誤的關鍵，而在診斷前使用不同的抗生素可能差距不如想像中的大。最後，雖然入住加護病房可以增加第四期癌症患者併敗血性休克患者的存活率，但是院內死亡率依然很高，因此完整的醫病溝通，依然是下相關醫療決策不可或缺的一環。

關鍵字

結核 ； 癌症 ； 預防醫學 ； 糖尿病 ； 加護病房

並列摘要

Introduction
Tuberculosis (TB) and cancer are two major global communicable and non-communicable diseases. In the field of public health, preventive medicine regarding these two diseases are important issues. We, therefore, targeted primary, secondary and tertiary prevention of these two important global diseases.
Materials and Methods
In primary prevention, we discussed whether diabetes mellitus (DM) was associated with higher risk of latent tuberculosis infection. In past studies, DM was found to increase risk of active TB and had impact on clinical outcome. The association between diabetes and latent tuberculosis infection (LTBI), however, was scant in studies. We used meta-analysis to discuss if diabetes was associated with risk of latent tuberculosis infection.
In secondary prevention, we discussed whether a newer fluoroquinolone (FQ), gemifloxacin, will lead to TB treatment delay. In the past, using FQs with effects on TB prior to TB diagnosis will lead to clinical improvement and cause treatment delay. Newer FQ, gemifloxacin, has little anti-TB effect and some have proposed that use of gemifloxacin prior to TB diagnosis would reduce TB treatment delay compared with other FQs. In this study, we recruited two cohorts from three hospitals in northern Taiwan and also from Taiwan national health insurance claims (NHI) database.
In tertiary prevention, we analyzed whether admission to intensive care unit (ICU) is beneficial to stage IV septic shock patients long-term survial. In past studies, a pessimistic attitude was held toward admitting late-stage cancer patients to ICU for septic shock management. Admission to ICU was considered futile, lead to patients suffering and did not bring much benefit to patients. As cancer and critical care treatment improved, current concepts have also gradually changed. In this study, we used linkage between Taiwan cancer registry and Taiwan NHI database for patients recruitment.
Results
In primary prevention, we included 13 studies with 38263 participants from 7 nations. We found that there was an association between diabetes mellitus and LTBI (OR:1.18(95% CI:1.06-1.30)). The association appeared to be lower than previously perceived.
In secondary prevention, we included 201 patients in the hospital-based cohort and 3544 patients in the population-based cohort. After propensity score matching, we found that there was no evidence that use of gemifloxacin leads to shorter TB treatment delay.
In tertiary prevention, we included 11825 stage IV cancer patients with septic shock. Among them, 6089 patients were admitted to ICU with an overall 70% in-hospital mortality rate. After PS matching, we found that admission to ICU was associated with better overall survival(HR: 0.76, 95% CI: 0.72-0.79), lower in-hospital mortality rate (OR: 0.61, 95% CI: 0.55-0.68) and better post-discharge long-term survival (HR: 0.77, 95% CI: 0.70-0.85).
Discussion and conclusions
Based on our study, we found that diabetes mellitus was associated with higher risk of LTBI. The risk, however, was not higher than expected and targeting DM patients for LTBI screening may need more consideration. For TB diagnosis, high clinical alertness and aggressive TB survey remain the key to reducing TB treatment delay. Using different antibiotics prior to TB diagnosis may make little difference. Last, though admission to ICU could improve stage IV cancer patients with septic shock survival rate, the in-hospital mortality remains high. Thorough and detailed communication between phyisicians, patients and families remained irreplaceable.

並列關鍵字

tuberculosis ； cancer ； preventive medicine ； diabetes mellitus ； intensive care unit

參考文獻

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