Nurse‐controlled analgesia (NCA) following major surgery in 10 000 patients in a children’s hospital

Background and Objectives: Patients who received NCA with morphine following major surgery between 1996 and 2008 at Great Ormond Street Hospital, London, UK, were prospectively studied in the postoperative period to determine effectiveness, morphine requirements, incidence of common side effects, and serious adverse events. Methods: The morphine NCA regimen and monitoring was according to standard hospital protocols. Data were collected prospectively and subsequently entered by trained personnel into a secure database. Patient demographics, effectiveness and satisfaction rates, morphine requirements, side effects, and serious complications were recorded. Results: 10 079 patients were included. The average age was 4 years old (range 1 day to 20.5 years, median 2.3 years). There were 510 neonates. The average NCA duration was 43.7 h. 1.8% of morphine NCAs were replaced by other methods because analgesia was unsatisfactory. Satisfaction ratings were ‘good’ or ‘very good’ for 98% of the remainder. Average daily morphine requirement (mcg·kg^?1·h^?1) was related to age, surgical category, and postoperative time. Side effects included PONV (25%), itching (9.4%), depression of respiration, and sedation (4.5%); incidences varied with age, morphine dose, and type of surgery. Serious, potentially life‐threatening adverse effects (SAE) were 0.4%. There were no deaths. SAE were significantly greater in neonates (2.5%), relative risk 9.4, P < 0.001. Morphine dose in neonates who experienced SAE was not significantly different from other neonates. Conclusion: NCA with morphine is an acceptable, safe, and effective method of postoperative analgesia for a wide range of ages and types of surgery in our practice. Morphine requirements increase with age, but there was also considerable inter‐individual variation within age groups. PONV, itching, sedation, and respiratory depression are expected side effects. SAE are uncommon but the incidence is greatest in neonates.     

新型含哌嗪侧链三唑类化合物的设计、合成和抗真菌活性研究

目的 基于唑类药物与靶酶相互作用模式,设计新型三唑类化合物,并测试其对常见致病真菌的抑制活性.方法 采用酰化反应合成目标化合物,通过1H NMR和MS确证其化学结构,经微量液基稀释法测试体外抗真菌活性.结果 合成了12个含C1甲基和哌嗪侧链的新型唑类化合物,它们均显示了中度至良好的抗真菌活性.结论 部分目标化合物对白色念珠菌的活性优于对照药氟康唑,值得进一步深入构效关系研究.     

Toxicity and side effects of hydroxyurea used for primary thrombocythemia

Over the last 20 years a vast array of data has been accumulated on the efficacy of hydroxyurea (HU) in patients with Philadelphia-negative myeloproliferative disorders (MPD). However, several side effects have been described as well. Besides many anecdotal reports, no evaluation of their prevalence and type exists in large series of treated patients. We report here the side effects of HU in a retrospective, single institution, cohort study of 152 patients suffering from MPD with thrombocytosis (median follow-up 8.13 years). In 6.5% of patients drug failure was registered. Unwanted side-effects (five symptomatic macrocytic anemia, two fever reactions, two allergic reactions, four cases each of leg painful ulcers, three acute leukemia or myelodysplasia) induced to withdraw therapy in 16 patients. Three cases of nail pigmentation were observed. In our experience, HU showed to be an effective and safe drug in most patients with MPD. Prompt recognition of side effects, which have been mostly minor and rapidly subsiding on drug withdrawal, is in any case crucial to avoid more severe complications.     

Minimal interference: A basis for selecting ART for prevention with positives

Given international interest in “treatment as prevention” (TasP) and the pertinence of optimizing antiretroviral treatment (ART) regimens for TasP, 19 French HIV experts were interviewed on their criteria for ART if used specifically for prevention with HIV-positive persons. Through content analysis of the interview material, nine criteria were identified. The most endorsed criteria, collectively, suggest a choice of treatment based on “minimal interference” where negative impacts of ART are minimized and ease of treatment integration maximized in the lives of people living with HIV/AIDS (PLHIV) for both the short and long term. These criteria were the tolerance, side effects, and/or toxicity profile of ART, simplicity (e.g., of treatment schedule, dosage form) and the individualization of treatment (e.g., adapted to lifestyle). While virologic efficacy (i.e., a durable, undetectable viral load) was also deemed important, several experts specified that it was virtually assured with current treatments. To a much lesser extent, experts endorsed diffusion of ART into the genital compartments, a strong genetic barrier (against resistance), validated treatments (as opposed to new classes of ART), a rapid reduction in HIV viral load, and treatment cost. Pharmacologically, minimal interference calls for further improvements in the tolerance, side effects and toxicity profile of ART and in the simplicity of ART administration. Clinically, it means avoiding a one-size-fits-all approach to ART in TasP and engagement with and of PLHIV in ART selection and side effects management. Strategically, it emphasises keeping the health and quality of life of PLHIV at the forefront of a TasP-oriented public health intervention.     

分析儿童颅内幕上原始神经胚层肿瘤的临床、影像学、病理及手术治疗

目的：探讨儿童颅内幕上原始神经胚层肿瘤的临床表现、影像学特点、病理特点及手术治疗方法。方法：回顾性分析于2000年1月～2012年1月在我院经手术与病理证实为儿童颅内原始神经胚层肿瘤的50例患儿的临床资料。结果：（1）临床表现,本组患儿临床表现均以癫痫发作、慢性颅内高压及神经功能损害为主;（2）影像学特点,CT及MRI显示肿瘤体积大,血供丰富,边界清晰,呈囊性变、瘤内出血,病灶周围水肿较轻或无水肿;（3）病理特点,原始神经胚层由小圆细胞组成,可见菊花团生成,免疫组化染色呈多向分化倾向;（4）手术治疗,本组患儿均实施显微外科术,全切除39例,次全切除11例,术后放疗40例．好转出院46例,死亡4例,平均生存12．5±6．7个月。结论：应结合临床表现、影像学特点、病理特点对儿童颅内幕上原始神经胚层肿瘤进行诊断,治疗首选手术切除,术后需进行放射治疗。     

国产齐拉西酮与维思通的临床对照治疗

目的对比国产齐拉西酮与维思通的疗效和不良反应.方法对60例精神分裂症患者随机分为国产齐拉西酮组30例和维思通组30例,进行相应的药物治疗,疗程6周,采用PANSS量表和TESS副反应量表进行评价.结果国产齐拉西酮和维思通疗效相当,但国产齐拉西酮的不良反应发生率和症状严重程度显著低于维思通,特别对催乳素和体重的影响明显较小,同时具有良好的依从性.结论国产齐拉西酮治疗精神分裂症疗效确切,不良反应少,依从性好.     

The safety of vandetanib for the treatment of thyroid cancer

ABSTRACT

Introduction: The tyrosine kinase inhibitor vandetanib was approved for use in 2012 for aggressive and symptomatic medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease. As the first effective systemic therapy for MTC, vandetanib is a major step forward and the phase III study suggests an important role for this agent. Trials have also been performed for its use in differentiated thyroid cancer (DTC) though it is not yet approved for use for this indication.

Areas covered: The efficacy and safety of vandetanib is discussed. Studies suggest improvement in progression-free survival (PFS) without clear overall survival benefit but with manageable low grade toxicities and improved quality of life on therapy.

Expert opinion: Vandetanib has an important role in the management of patients with progressive metastatic MTC. The use in patients with stable or asymptomatic disease has no proven benefit. The side effects can usually be managed with dose reduction, interruption, and/or specific symptomatic therapy.     

Safety and side effects of the acne drug,oral isotretinoin

Isotretinoin is a very effective medication for the treatment of severe recalcitrant acne. However, its use is associated with many side effects, some of which can be very serious. The most important issue is its teratogenicity, which has resulted in new pregnancy prevention policies and programmes implemented by the manufacturer. Recently, the association of isotretinoin with depression has been recognised and new guidelines have been adopted for this possible side effect. The most common adverse events, observed during treatment, are mucocutaneous and ophthalmological. In addition, laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary and other systems have been described.     

The safety of levetiracetam

Levetiracetam is an antiepileptic drug approved for use as an adjunct agent in partial-onset seizures in adults and children aged ≥ 4 years. It was also approved as adjunctive therapy in the treatment of adults and adolescents aged ≥ 12 years with juvenile myoclonic epilepsy. A parenteral intravenous formulation has recently become available allowing for its use when oral administration is temporarily not feasible. Available literature has demonstrated and supported that levetiracetam has an acceptable safety profile and this review discusses the safety profile of levetiracetam, with attention to special populations. The most common adverse effects are somnolence, asthenia and dizziness, which usually appear early after initiation of levetiracetam therapy and generally resolve without medication withdrawal. The most serious adverse effects are behavioral in nature and are more common in children and in patients with a prior history of behavioral problems.