鞘注微量長春新堿污染的甲氨蝶呤或阿糖胞苷不良事件研究
發(fā)布時(shí)間：2018-11-24 20:29
【摘要】：目的：查明甲氨蝶呤、阿糖胞苷不良事件的原因；描述甲氨蝶呤、阿糖胞苷不良事件病例的臨床特點(diǎn)；初步評(píng)價(jià)病例治療效果和預(yù)后情況；總結(jié)調(diào)查過程中發(fā)現(xiàn)的問題,為預(yù)防控制該類藥物不良事件的發(fā)生提供重要參考。 方法：通過建立監(jiān)測系統(tǒng),收集在2007年1月1日～9月30日期間進(jìn)行鞘內(nèi)注射治療后出現(xiàn)雙下肢漸進(jìn)性無力、蹲立困難或有尿便功能障礙等癥狀的患者資料。采用描述流行病學(xué)方法分析不良事件的時(shí)間、人群、地點(diǎn)分布。對(duì)華聯(lián)藥廠進(jìn)行現(xiàn)場調(diào)查,收集藥品生產(chǎn)環(huán)節(jié)、原料來源和藥品流向等資料。使用回顧性隊(duì)列研究方法選取16家發(fā)生不良事件病例的醫(yī)院內(nèi)的鞘內(nèi)注射化療人群作為研究隊(duì)列,收集研究對(duì)象的相關(guān)資料,計(jì)算不同人群的相對(duì)危險(xiǎn)度。運(yùn)用超高效液相色譜儀檢測甲氨蝶呤和阿糖胞苷樣品中長春新堿的含量。運(yùn)用文獻(xiàn)系統(tǒng)評(píng)價(jià)法對(duì)既往誤行鞘注長春新堿的病例報(bào)道進(jìn)行綜合分析。使用聚類分析描述不良病例的臨床特征和疾病嚴(yán)重程度。選擇部分不良事件病例,對(duì)患者預(yù)后情況及其影響因素進(jìn)行分析。 結(jié)果：截止到2007年9月27日,甲氨蝶呤、阿糖胞苷不良事件監(jiān)測系統(tǒng)共收集了192例患者。其中男性121例,女性71例。病例主要集中在30歲以下,占所有病例的76%,所有患者均為白血病、淋巴瘤和絨毛膜癌的患者。不良事件病例發(fā)病時(shí)間分布在2007年6月12日至9月11日之間。鞘注問題批號(hào)Ara-C070401B發(fā)病率最高,為100%；鞘注其它問題批號(hào)分別為Ara-C070401A、MTX070405B和MTX070403A,其發(fā)病率依次為76%、50%和42%。對(duì)147例不良事件患者進(jìn)行了核實(shí)診斷,不良事件病例臨床癥狀表現(xiàn)為雙下肢乏力(100%),蹲立困難(100%),肌力減退性加重(100%),嚴(yán)重時(shí)完全癱瘓(19.7%),多數(shù)有尿便功能障礙(59.2%)。 上海華聯(lián)藥廠將長春新堿、甲氨蝶呤和阿糖胞苷在同一生產(chǎn)線上生產(chǎn)。問題批號(hào)藥品均在長春新堿之后生產(chǎn)。 采集的樣品中,問題批號(hào)藥品均檢測出長春新堿,含量在0.28～18ug之間。劑量反應(yīng)關(guān)系分析結(jié)果顯示：鞘注長春新堿劑量越高,人群發(fā)病率的相對(duì)危險(xiǎn)度越高。由BMDS軟件推算出當(dāng)混入鞘內(nèi)的長春新堿的劑量高于0.02ug時(shí),不良事件發(fā)病率為1‰。 對(duì)147例不良事件患者進(jìn)行聚類分析,聚類分析將147例患者分成了輕中重型病例。對(duì)鞘注長春新堿的劑量與病情程度的統(tǒng)計(jì)分析結(jié)果顯示鞘注劑量與病情嚴(yán)重程度有關(guān)(F=8.06,P=0.00) 對(duì)既往誤行鞘注長春新堿事件的病例報(bào)道系統(tǒng)評(píng)價(jià)結(jié)果發(fā)現(xiàn),外科治療使用腦室-腰椎腦脊液灌注引流術(shù)(χlog rank2=11.49,P=0.00)、谷氨酸(χlog rank2=7.47,P=0.00)和葉酸(χlog rank2=5.07,P=0.02)可以提高患者的生存時(shí)間。 29例不良事件患者預(yù)后隨訪研究結(jié)果顯示采取多重治療方式后,38%的患者肌力有恢復(fù),但是預(yù)后仍然不良：2死于原發(fā)病,22例肌肉萎縮,9例完全性截癱,24例行走困難。 結(jié)論：①木次不良事件的原因是問題批號(hào)的甲氨蝶呤和阿糖胞苷混入了微量長春新堿,患者鞘內(nèi)注射后引起神經(jīng)損害；②不良事件病例,短期預(yù)后不良,應(yīng)積極采取一些措施改善病例預(yù)后。
[Abstract]:Objective: To find out the causes of the adverse events of methotrexate and absaccharin, and to describe the clinical features of the cases of methotrexate and absaccharin, and to evaluate the curative effect and the prognosis of the case. The problems found during the investigation are summarized. An important reference is provided to prevent the occurrence of adverse events in the control of the drug. Methods: Through the establishment of the monitoring system, the patients with double lower limb progressive weakness, difficulty in squatting, or dysfunction of the urine and the like were collected in the period from 1 January to 30 September 2007. Data. Time, population, location, Distribution. Carry out on-site investigation of Hualian pharmaceutical factory, collect drug production link, raw material source and drug flow direction, etc. Data. A retrospective cohort study was used to select the intraventricular injection chemotherapy population in 16 patients with adverse event cases as the study cohort, to collect relevant information from the study subjects, to calculate the relative risk of the different populations Determination of Vincristine in Methotrexate and Asaccharin Samples by Ultra-High Performance Liquid Chromatography Content: A comprehensive review of the case reports of previously misdirected vincristine with the literature system evaluation method Analysis. The clinical features and the severity of the disease were described using cluster analysis Degree. Select a part of the adverse event case and the patient's prognosis and its influencing factors Analysis. Results: As of 27-Sep-2007, a total of 1 was collected by the treatment system for methotrexate and Asaccharin adverse events. 92 patients, of whom 121 were male, 71 cases of women. The case was mainly concentrated under the age of 30, accounting for 76% of all cases, and all the patients were leukemia, lymphoma and villus. Patients with membrane cancer. The incidence of adverse events was distributed between 12 and September 2007 11 days. The highest incidence of Lot No. Ara-C070401B was the highest, with 100%. The number of other issues for the injection was Ara-C070401A, MTX070405B, and MTX070403A, with an incidence of 76%, 50, respectively.% and 42% of the 147 patients with adverse events were verified and diagnosed. The clinical symptoms of the adverse events were two lower limbs (100%), squat (100%), hypodynamia (100%), and severe total paralysis (19.7%), most of which had urinary dysfunction (5 9. 2%). The Shanghai Hualian Pharmaceutical Co., Ltd. Production on the same production line. The drug of the lot number is in the same production line. After vincristine production. In the collected samples, the problem lot number drug was tested for vincristine, with a content of The results of the analysis of the dose response showed that the higher the dose of vincristine, the higher the dose of vincristine. The higher the relative risk of morbidity. The incidence of adverse events was 1%. Cluster analysis was performed on 147 patients with adverse events, and the cluster analysis will be 1. 47 patients were divided into light and medium-duty cases. The statistical analysis of the dose and severity of the injected vincristine showed that the injection dose was related to the severity of the condition (F = 8.06, P = 0. 00) The results of the case report system evaluation of the new base event found that the surgical treatment was performed using a ventricular-lumbar spinal fluid perfusion drainage (log rank2 = 11.49, P = 0. 00), glutamic acid (log rank2 = 7.47, P = 0. 00), and folic acid (Prolog rank2 = 5.07, P = 0. 02) The survival time of the patient could be increased. The outcome of the follow-up study of 29 patients with adverse events showed that 38% of the patients had the recovery of the muscle strength after the multiple treatment, but the prognosis was still poor: 2 died in the original disease and 22 cases Muscular atrophy, 9 complete paraplegia, 24 routine walking difficulties. Conclusion: The cause of the adverse events is that methotrexate and Asaccharin of the lot number are mixed with a trace of vincristine, which causes nerve damage after intraoral injection of the patient; and case of adverse events.
【學(xué)位授予單位】：中國疾病預(yù)防控制中心
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2009
【分類號(hào)】：R181.35
本文編號(hào)：2354946
[Abstract]:Objective: To find out the causes of the adverse events of methotrexate and absaccharin, and to describe the clinical features of the cases of methotrexate and absaccharin, and to evaluate the curative effect and the prognosis of the case. The problems found during the investigation are summarized. An important reference is provided to prevent the occurrence of adverse events in the control of the drug. Methods: Through the establishment of the monitoring system, the patients with double lower limb progressive weakness, difficulty in squatting, or dysfunction of the urine and the like were collected in the period from 1 January to 30 September 2007. Data. Time, population, location, Distribution. Carry out on-site investigation of Hualian pharmaceutical factory, collect drug production link, raw material source and drug flow direction, etc. Data. A retrospective cohort study was used to select the intraventricular injection chemotherapy population in 16 patients with adverse event cases as the study cohort, to collect relevant information from the study subjects, to calculate the relative risk of the different populations Determination of Vincristine in Methotrexate and Asaccharin Samples by Ultra-High Performance Liquid Chromatography Content: A comprehensive review of the case reports of previously misdirected vincristine with the literature system evaluation method Analysis. The clinical features and the severity of the disease were described using cluster analysis Degree. Select a part of the adverse event case and the patient's prognosis and its influencing factors Analysis. Results: As of 27-Sep-2007, a total of 1 was collected by the treatment system for methotrexate and Asaccharin adverse events. 92 patients, of whom 121 were male, 71 cases of women. The case was mainly concentrated under the age of 30, accounting for 76% of all cases, and all the patients were leukemia, lymphoma and villus. Patients with membrane cancer. The incidence of adverse events was distributed between 12 and September 2007 11 days. The highest incidence of Lot No. Ara-C070401B was the highest, with 100%. The number of other issues for the injection was Ara-C070401A, MTX070405B, and MTX070403A, with an incidence of 76%, 50, respectively.% and 42% of the 147 patients with adverse events were verified and diagnosed. The clinical symptoms of the adverse events were two lower limbs (100%), squat (100%), hypodynamia (100%), and severe total paralysis (19.7%), most of which had urinary dysfunction (5 9. 2%). The Shanghai Hualian Pharmaceutical Co., Ltd. Production on the same production line. The drug of the lot number is in the same production line. After vincristine production. In the collected samples, the problem lot number drug was tested for vincristine, with a content of The results of the analysis of the dose response showed that the higher the dose of vincristine, the higher the dose of vincristine. The higher the relative risk of morbidity. The incidence of adverse events was 1%. Cluster analysis was performed on 147 patients with adverse events, and the cluster analysis will be 1. 47 patients were divided into light and medium-duty cases. The statistical analysis of the dose and severity of the injected vincristine showed that the injection dose was related to the severity of the condition (F = 8.06, P = 0. 00) The results of the case report system evaluation of the new base event found that the surgical treatment was performed using a ventricular-lumbar spinal fluid perfusion drainage (log rank2 = 11.49, P = 0. 00), glutamic acid (log rank2 = 7.47, P = 0. 00), and folic acid (Prolog rank2 = 5.07, P = 0. 02) The survival time of the patient could be increased. The outcome of the follow-up study of 29 patients with adverse events showed that 38% of the patients had the recovery of the muscle strength after the multiple treatment, but the prognosis was still poor: 2 died in the original disease and 22 cases Muscular atrophy, 9 complete paraplegia, 24 routine walking difficulties. Conclusion: The cause of the adverse events is that methotrexate and Asaccharin of the lot number are mixed with a trace of vincristine, which causes nerve damage after intraoral injection of the patient; and case of adverse events.
【學(xué)位授予單位】：中國疾病預(yù)防控制中心
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2009
【分類號(hào)】：R181.35
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