1例头孢地尼分散片致自身免疫性溶血性贫血案例分析

目的：探讨头孢地尼分散片致自身免疫性溶血性贫血（AIHA）的诊断及治疗。方法：分析1例头孢地尼分散片致AIHA患者的诊疗经过，结合文献检索，探索头孢地尼分散片诱发AIHA的机制及应对措施。结果：患儿口服头孢地尼分散片1 d后发生AIHA，立即停用，给予注射用甲泼尼龙琥珀酸钠抑制免疫反应，5%碳酸氢钠碱化尿液、吸氧等对症治疗，并于停药后1周溶血得到控制。结论：儿童临床使用头孢地尼时，需密切关注患者是否有溶血临床表现，以便及时发现问题，及时采取适当的处理措施，以保证患者的用药安全     

注射用头孢曲松钠治疗感染性心内膜炎致药物热1例

1例66岁男性患者因感染性心内膜炎使用注射用头孢曲松钠等抗感染治疗,在使用注射用头孢曲松钠第13天后出现体温正常后再发热,血培养、超声及CT检查未见感染未控制或新发感染依据,停用注射用头孢曲松钠后,患者体温恢复正常。注射用头孢曲松钠致药物热明确。     

Early‐Onset 5‐Fluorouracil Toxicity in a Patient Negative for Dihydropyrimidine Dehydrogenase Mutations: The Clinical Course of Reversal with Uridine Triacetate

An antimetabolite pyridine analog, 5‐fluorouracil (5‐FU), is used to treat solid tumors. Early toxicities may occur at standard doses of 5‐FU due to dihydropyrimidine dehydrogenase (DPD) deficiency. Uridine triacetate, approved by the Food and Drug Administration in 2015, is an oral prodrug of uridine, a pharmacologic antidote for 5‐FU toxicity. To our knowledge, this is the first case report that documents the clinical course of a patient treated with uridine triacetate to reverse early‐onset 5‐FU toxicity negative for DPD mutations. We describe the case of a 73‐year‐old man with anal cancer treated with standard‐of‐care chemotherapy and radiation. Two days after completion of his initial 5‐FU infusion, the patient developed severe mucositis and extreme fatigue, followed by a rapid decline in his blood cell counts and fevers. The patient was initiated on uridine triacetate 86 hours after completion of his 5‐FU infusion. Over a 10‐day hospital length of stay, the patient's absolute neutrophil count recovered to within normal limits, and his mucositis significantly improved. At follow‐up visits, the patient denied any residual symptoms of 5‐FU toxicity. We describe the patient's clinical course from hospital presentation to 31 days after initiation of uridine triacetate.     

The relationship between computerized physician order entry and pediatric adverse drug events: a nested matched case‐control study

This study assesses the impact of computerized physician order entry (CPOE) implementation in pediatric hospitals on reported adverse drug events. Using a nested matched case‐control design; we linked CPOE implementation information from the health information management systems society analytics database with reported adverse drug event (ADE) from the national association of children's hospitals and related institutions case mix comparative data program. Differences were examined using univariate and multivariate conditional logistic regression analyses. Patients from CPOE hospitals were more frequently seen in larger hospitals have more co‐morbidities than those from non‐CPOE hospitals. When matched by admitting diagnosis, age, gender and race, ADE cases were associated with more reported co‐morbidities, and were reported less frequently in hospitals with CPOE. Patients from hospitals without CPOE were 42% more likely to experience reportable ADE after adjusting for the presence of co‐morbidities. In conclusion, we found significant beneficial associations between reportable ADE and CPOE adoption in a representative sample of pediatric hospitals. Copyright © 2009 John Wiley & Sons, Ltd.     

A Rare Case of Levetiracetam and Drug-Induced Idiopathic Aseptic Meningitis in a Pediatric Patient

Levetiracetam (LEV) is a pyrrolidine derivative antiepileptic medication used for the treatment of seizures in pediatric and adult patients. We report a case of probable LEV-induced aseptic meningitis in a 13-year-old girl. The patient received LEV for a generalized seizure disorder and presented with symptoms 5 days after medication initiation. Ten days after LEV initiation, the patient presented to the hospital for further management. During her hospital course, infectious etiologies were ruled out with clinical and diagnostic testing. Upon discontinuation of LEV, the patient's symptoms resolved. Although select antiepileptic medications have been associated with drug-induced aseptic meningitis (DIAM), to date, no reports have been published about DIAM following the administration of LEV. We describe and categorize the probability of DIAM in association with LEV, as observed in a patient case.     

信迪利单抗致1例多系统免疫相关不良事件

对1例信迪利单抗在用药两周期后引起甲状腺功能异常、免疫相关性肠炎及肝功能损害进行讨论分析.该患者诊断为信迪利单抗治疗后引起的多系统免疫相关不良事件.予以激素冲击治疗,以左旋甲状腺激素替代治疗后,患者症状好转.     

1例老年COPD急性加重患者多药联用致震颤的诊治分析

目的 临床药师通过分析多种药物联用导致不良反应的药物因素,为患者安全用药提供依据。方法 临床药师对1例老年COPD急性加重患者治疗中出现震颤的可能药物因素进行分析,调整药物治疗方案。结果 医师接受并调整用药方案后,患者未再出现震颤和其他药物不良反应,病情好转出院。结论 临床药师具有处置药物不良反应的专业优势,从药学角度提供科学的依据,协助医师制订最佳用药方案,发挥医疗团队的协同作用,使患者获得优质的医疗服务。     

Anakinra‐Induced Acute Liver Failure in an Adolescent Patient with Still's Disease

The interleukin‐1 (IL‐1) family consists of 11 cytokines that play key regulatory roles in many immune and inflammatory processes. Anakinra (Kineret, Amgen, Inc.) is an IL‐1 receptor antagonist (IL‐1ra). Increased levels of IL‐1 are found in several disease states suggesting that anakinra may be beneficial in disorders associated with elevated IL‐1 levels. Anakinra has been effectively used in the treatment of systemic juvenile idiopathic arthritis and adult‐onset Still's disease (AOSD). Despite its therapeutic benefits, anakinra also has potential side effects, including hepatotoxicity. We present a case of AOSD in an adolescent male that was treated with anakinra. During treatment, the patient developed acute liver failure that resolved upon withdrawal of anakinra. Although anakinra‐induced liver injury has been reported in adults, including one case of subacute liver failure, we believe our case is the first to show severe acute liver failure in an adolescent treated with anakinra. This case provides significant insight into a potentially serious complication associated with anakinra. It is important to further delineate these complications as the treatment indications for this drug expand.     

Phase II Study of Perifosine in Previously Untreated Patients with Metastatic Melanoma

Summary Purpose: To assess the response rate and toxicity of the alkylphosphocholine analogue, perifosine, in patients with metastatic or recurrent malignant melanoma. Patients and Methods: Patients had histologically proven, unidimensionally measurable disease which was incurable by standard therapy. Prior adjuvant immunotherapy was allowed but patients had not received prior chemotherapy. Perisfosine was given orally as a loading dose of 900 mg on day 1 followed by a maintenance dose of 150 mg po on days 2–21 in a 28 day cycle. The loading dose was 300 mg on day 1 of all subsequent cycles. Tumour response was assessed every 2 cycles. Results: 18 patients were accrued over 7 mos. No objective responses occurred in the 14 evaluable patients. Three patients (21%) achieved stable disease after 2 cycles and 11 had progression. Seventeen patients were evaluable for toxicity. Grade 3 or 4 non-hematologic toxicities included: diarrhea (12%), arthralgia (12%), nausea (6%), headache (6%), and fatigue (6%). No grade 3 or 4 hematological or biochemical toxicity were observed. Seventy-seven percent of patients received ≥90% of planned cycle 1 dose intensity and 58% received ≥90% of planned dose for cycle 2+. Four patients required dose reductions; treatment was delayed in 5 patients; and 5 patients missed doses because of toxicity. Conclusions: Perifosine can be safely administered when given as an initial loading dose followed by daily maintenance therapy over 28 days. Gastrointestinal toxicity is common but generally of low grade. Hematological toxicity is minimal. No objective responses were observed. No further development of single-agent perifosine is recommended in malignant melanoma.     

Nephrotoxicity Associated with Concomitant Use of Ledipasvir‐Sofosbuvir and Tenofovir in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection

Direct‐acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, with superior efficacy and safety compared to interferon‐based therapies. Despite these improvements, drug interactions with DAAs exist and may be clinically relevant in human immunodeficiency virus (HIV)‐coinfected patients. We present a case of nephrotoxicity associated with concomitant use of tenofovir disoproxil fumarate (TDF) and ledipasvir‐sofosbuvir (LDV‐SOF). A 56‐year‐old woman with HIV infection who had been taking efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) for 6 years developed acute kidney injury 8 weeks after initiating LDV‐SOF for the treatment of HCV infection. Her serum creatinine concentration peaked at 10 mg/dL, compared with her baseline concentration of 0.9–1 mg/dL. Kidney biopsy revealed acute tubular necrosis and acute interstitial nephritis. Both LDV‐SOF and TDF were discontinued, and the patient's serum creatinine concentration decreased to 1.3 mg/dL over the following 6 weeks. We postulate that this adverse drug reaction may have been secondary to the known interaction between ledipasvir and TDF, which results in increased TDF exposure. Despite knowledge of this interaction, LDV‐SOF is commonly prescribed in patients with HIV‐HCV coinfection, as patients who received LDV‐SOF– and TDF‐containing regimens in trials have not demonstrated adverse clinical consequences related to this interaction. This case highlights the rare but potentially serious nephrotoxicity that can result from TDF toxicity and serves as a reminder to clinicians to implement close renal function monitoring in patients receiving both LDV‐SOF and TDF. Clinicians prescribing LDV‐SOF to HCV‐HIV–coinfected patients receiving TDF should be cautious about use with concomitant nephrotoxic medications and monitor markers of tubular dysfunction, including urinary phosphorus excretion, and renal injury at baseline and week 4 of therapy. Tenofovir alafenamide and alternative DAAs may also have a role in the management of patients at high risk for renal adverse effects from TDF.     

Adverse events following statin–fenofibrate therapy versus statin alone: A meta‐analysis of randomized controlled trials

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1 例布洛芬混悬液致儿童重症多形红斑报道并布洛芬严重不良反应文献复习

目的:探讨布洛芬混悬液与重症多形红斑的相关性,为布洛芬的安全使用提供参考。 方法:分析 1 例布洛芬混悬液导致重症多形红斑的病例,并进行文献复习。 结果:根据国家药品不良反应中心药品不良反应/ 事件关联性评价标准,布洛芬混悬液引起重症多形红斑的可能性较大。 查阅文献,布洛芬引起的皮肤不良反应大多为轻型药疹,罕见重型药疹,也有布洛芬引起多形红斑、Stevens-Johnson 综合征、中毒性表皮坏死松解症、剥脱性皮炎、超敏反应综合征等严重皮肤不良反应的个例报道。 结论:布洛芬临床应用广泛,耐受性好,但需警惕其严重皮肤不良反应。     

Synthesis and SAR Studies of Dual AKT/NF‐κB Inhibitors Against Melanoma

The protein Kinase B alpha (AKT) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathways are central regulators of cellular signaling events at the basis of tumor development and progression. Both pathways are often up‐regulated in different tumor types including melanoma. We recently reported the identification of compound 1 (BI‐69A11) as inhibitor of the AKT and the NF‐κB pathways. Here, we describe SAR studies that led to novel fluorinated derivatives with increased cellular potency, reflected in efficient inhibition of AKT and IKKs. Selected compounds demonstrated effective toxicity on melanoma, breast, and prostate cell lines. Finally, a representative derivative showed promising efficacy in an in vivo melanoma xenograft model.