The burden of HCV treatment in patients with inherited bleeding disorders

Summary. Many patients with inherited bleeding disorders are infected with hepatitis C virus (HCV). Antiviral treatment, consisting of pegylated interferon and ribavirin, has many side‐effects. The aim of the study was to prospectively assess the occurrence and course of side‐effects and changes in health‐related quality of life (HRQoL) during antiviral treatment in patients with inherited bleeding disorders and chronic HCV. Forty‐seven patients were followed during antiviral treatment. Side‐effects of treatment were recorded, and the Beck Depression Inventory and the RAND‐36 HRQoL questionnaire were administered at regular intervals. Frequently reported side‐effects were fatigue (100%), headache (94%), pruritus and skin rash (94%), concentration problems (89%), decreased appetite (89%), fever, irritability and hair loss (all 85%). Many side‐effects disappeared soon after end of treatment, but 4 weeks after cessation fatigue, concentration problems and sleeping problems were still present in more than 30% of patients. Dose reduction was necessary in 21 patients (45%), mostly because of decreasing weight or haemoglobin levels. Two patients stopped treatment prematurely because of side‐effects. Depression was present in 28 patients (60%). HRQoL decreased significantly during treatment in all RAND‐36 domains, and increased again within 4 weeks after treatment. Major side‐effects were similar in patients with successful (n = 31, 66%) and unsuccessful antiviral treatment. In patients with inherited bleeding disorders and chronic HCV, antiviral treatment has many, but mostly transient side‐effects and a significant impact on quality of life. Careful follow‐up and management of side‐effects will ensure optimal compliance and treatment results.     

Evaluation of beam hardening and photon scatter by brass compensator for IMRT

When a brass compensator is set in a treatment beam, beam hardening may take place. This variation of the energy spectrum may affect the accuracy of dose calculation by a treatment planning system and the results of dose measurement of brass compensator intensity modulated radiation therapy (IMRT). In addition, when X-rays pass the compensator, scattered photons are generated within the compensator. Scattered photons may affect the monitor unit (MU) calculation. In this study, to evaluate the variation of dose distribution by the compensator, dose distribution was measured and energy spectrum was simulated using the Monte Carlo method. To investigate the influence of beam hardening for dose measurement using an ionization chamber, the beam quality correction factor was determined. Moreover, to clarify the effect of scattered photons generated within the compensator for the MU calculation, the head scatter factor was measured and energy spectrum analyses were performed. As a result, when X-rays passed the brass compensator, beam hardening occurred and dose distribution was varied. The variation of dose distribution and energy spectrum was larger with decreasing field size. This means that energy spectrum should be reproduced correctly to obtain high accuracy of dose calculation for the compensator IMRT. On the other hand, the influence of beam hardening on k_Q was insignificant. Furthermore, scattered photons were generated within the compensator, and scattered photons affect the head scatter factor. These results show that scattered photons must be taken into account for MU calculation for brass compensator IMRT.     

国内儿童应用托吡酯安全性的文献分析

目的了解国内儿童应用托吡酯的不良反应（ADR）发生情况及其相关因素。方法计算机检索中国知网（CNKI）文献数据库,收集国内关于抗癫痫药物托吡酯用于儿童的临床研究文献,由2位研究者采用统一的资料提取表格,提取纳入文献中ADR病例的原患疾病,托吡酯用药剂量,ADR病例的性别及年龄,ADR出现时间、类型、处理及转归等资料。对儿童应用托吡酯导致的ADR及其相关因素采用SPSS16.0统计学软件进行数据分析。结果经文献检索,最终符合本研究纳入标准的关于儿童托吡酯ADR的研究文献共计22篇,关于托吡酯疗效的研究文献共计110篇,共计纳入13 011例患儿,其中2 771例发生ADR,ADR发生率为21.3%。关于托吡酯ADR的研究中,55.1%的ADR涉及神经及精神系统（泌汗障碍、影响自主神经功能等）,34.5%涉及内分泌系统（影响骨代谢及生长发育等）;关于托吡酯疗效的研究文献报道的ADR中,35.2%涉及神经及精神系统（出汗减少、记忆力下降、注意力不集中、头昏等）,27.1%涉及消化系统（食欲下降、胃肠道反应等）,19.5%为全身反应（体质量下降、发热等）。99.6%的儿童应用托吡酯发生的ADR的严重程度为Ⅲ-Ⅳ级,多数在降低托吡酯剂量或停药后症状减轻。结论本研究纳入的132篇关于儿童应用托吡酯发生ADR的研究文献中,均未提示重大ADR发生,但由于受到研究设计和样本量局限,同时,纳入本研究的关于ADR的文献,均存在关键信息不完整、研究报告质量欠佳等情况,因此建议进一步对儿童应用托吡酯开展上市后循证再研究及再评价,以确保临床用药安全。儿童应用托吡酯治疗导致的ADR及药物安全性问题,有待以后高质量、大样本、多中心的随机对照研究进一步证实。     

Rotarod Impairment: Catalepsy-Like Screening Test for Antipsychotic Side Effects

Extrapyramidal motoric symptoms are casual side effects under antipsychotic medication. New generation antipsychotics are expected to have a reduced risk due to different receptor affinities. Here, haloperidol and the new generation antipsychotics, risperidone, amisulpride, and aripiprazole, were examined with both catalepsy test and rotarod performance test to screen for their usability in mice. Mice treated with haloperidol, risperidone, and aripiprazole showed dose and time-dependent impairment. Amisulpride-treated mice showed no signs of catalepsy. Catalepsy test and rotarod performance test were useful methods to detect side effects of both generation antipsychotics. Catalepsy test provided more specificity whereas the rotarod test provided higher degree of sensitivity to motor impairment including catalepsy.     

Gastrointestinal side effects of NSAIDs – pharmacoeconomic implications

NSAIDs are frequently used as analgesics. They have a high incidence of GI adverse effects that have both social and economic costs. These costs impose a considerable strain on healthcare resources. This review discusses the epidemiology and economic cost of these adverse GI events. It also highlights the variability in risk and the impact of newer drugs. Risk stratification and the subsequent guided use of NSAIDs is likely to limit the pharmacoeconomic implications.     

Ocular surface frostbite secondary to ethyl chloride spray

Context: Ethyl chloride (EC) is a fast-acting vapo-coolant spray that provides rapid, transient, local analgesia for minor invasive procedures. Although the application of EC has decreased, it can be used as a cryoanalgesic agent in minor surgical procedures. Objective: Despite the widespread use of EC as a local anesthetic, there are few reported cases of serious adverse side effects. Material and methods: We report a 67-year old otherwise healthy man who underwent excision of a papilloma on his superior right eyelid by a general practitioner at a primary care center. The lesion was removed by curettage after slight freezing with EC spray. This chemical agent was applied without the adequate eye protection, and eight hours later the patient presented an acute frost injury of ocular surface. Results: Urgent treatment included copious irrigation of the affected eye, especially the conjunctival fornices, corticosteroid (prednisone) and antibiotic (neomycin) ointment. A week later, the eyelid lesion and keratoconjunctivitis had resolved but evidence of early cicatrization involving the inferior conjucntival fornix and symblepharon formation were present. Discussion: To the best of our knowledge, this is the first reported case of an acute burn of the ocular surface following EC spray exposure. Conclusion: EC should be avoided for short-term local anesthesia in the periocular region to prevent this serious complication.     

Long-term side effects of glucocorticoids

ABSTRACT

Introduction: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible.

Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment.

Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.     

HRQoL changes,mood disorders and satisfaction after treatment in an unselected population of patients with lung cancer

Objectives: This study intended to explore the impact of the first treatment modality on health‐related quality of life (HRQoL), mood disorders and mastery in an unselected population of patients with primary lung cancer and to judge patient satisfaction with treatment. Materials and Methods: An unselected group of 479 patients with newly diagnosed lung cancer in Southern Norway (Agder counties) were included prospectively from June 2002 to June 2005, collecting data on histology, treatment options, HRQoL, mood disorders and mastery at baseline as well as satisfaction with treatment, and changes in HRQoL and mood disorders after finishing the first treatment modality. Results: After finishing the first treatment modality, patients experienced a worsening of nine HRQoL parameters and an improvement in one. Patients in good performance status experienced reduced physical and role function, and if in reduced performance, improved emotional and role function. Patients with mood disorders experienced reduced anxiety and depression, anxious patients experienced reduced neuropathies, and depressed patients experienced improved social functioning and appetite. Half of the patients treated actively were definitely positive to repeat the same treatment again compared with only 15% in the best supportive care group. Surgery was associated with reduced role function and increased dyspnoea, radiation was associated with increased fatigue, and chemotherapy in small cell lung cancer (SCLC), to a larger extent, was associated with alopecia than in non‐SCLC (NSCLC). Conclusion: The development of many HRQoL parameters after the first treatment modality in an unselected population of patients with primary lung cancer seemed, at large, well correlated to general disease progression and to well‐known treatment side effects. However, reduced role function after lung surgery, and reduced anxiety and depression in patients with mood disorders at baseline might be surprising. Patient satisfaction with treatment was surprisingly good. Several findings in this study may help clinicians to improve their handling of patients with lung cancer. Please cite this paper as: Rolke HB, Bakke PS and Gallefoss F. HRQoL changes, mood disorders and satisfaction after treatment in an unselected population of patients with lung cancer. The Clinical Respiratory Journal 2010; 4: 168–175.     

Mechanism of inhibitory effect of glucagon on gastrointestinal motility and cause of side effects of glucagon

Glucagon is commonly used during gastrointestinal examinations for the temporary inhibition of gastroduodenal movements. Three preparations of glucagon are now clinically available: those prepared by extraction from the pancreas (GL-P), by chemical synthesis (GL-S), and by genetic recombination (GL-G). The aim of this study was examine the mechanism of the inhibitory effect of glucagon on gastrointestinal motility and the cause of its side effects by comparing three glucagon preparations. In four conscious dogs, gastrointestinal contractions were monitored by means of chronically implanted force transducers. Each glucagon preparation (GL-P [15 μg/kg], GL-S [5, 15, 45 μg/kg], GL-G [15 μg/kg]), scopolamine butylbromide (0.4 mg/kg), or saline was administered intravenously 20 min after the termination of spontaneous phase III contractions, and blood samples were taken at 5- to 10-min intervals. Barium was administered into the stomach 10 min after the infusion of each drug. The arrival of a barium meal in the stomach immediately stimulated gastrointestinal contractions, and the barium meal was expelled into the duodenum and jejunum from the stomach. Intravenous injection of 15 μg GL-S first stimulated duodenal contractions that propagated to the jejunum, followed by strong inhibition of the barium-induced gastrointestinal contractions. This inhibitory effect of glucagon and the activity of the glucagon-induced duodenal contractions were dose-related. The inhibitory effects of GL-G and GL-S were stronger than that of GL-P. Blood glucose and plasma insulin concentrations were raised after intravenous injection of each glucagon preparation, but there was no difference among the three preparations and no dose relationship. The inhibitory effects of glucagon depend on the material purity and dose, and the inhibitory mechanism was independent of any effect on carbohydrate metabolism. Glucagon administration caused phase III-like contractions in the duodenum and jejunum, which may be responsible for the side effects of glucagon. (Received Jan. 8, 1998; accepted June 26, 1998)