Adverse drug reactions: physicians' opinions versus a causality assessment method

Since spontaneous reporting of adverse drug reactions depends on the physician's opinion of the relationship between the drug and the adverse event, we compared physicians' opinions with the scores obtained by the causality assessment method used in France. During a 2 month period, all physicians who reported adverse drug reactions (ADRs) to our pharmacovigilance centre expressed their opinions on the causal link by means of visual analogue scales. ADR reports were then assessed with the French causality assessment method by a clinical pharmacologist who was blind to physicians' opinions.The assessment by both physicians and the standardized method was performed for 75 ADR cases involving 120 drugs. Physicians used a wide range of assessments, with a preponderance of extreme scores, resulting in a U-shaped distribution, while the standardized method gave generally low scores. Scores given by physicians were very high (causality considered very likely or likely) in 60% of cases and very low (causality considered unlikely or dubious/possible) in 32% of cases. Scores obtained using the causality assessment method were low (causality dubious/possible) in 89% of cases and causality considered likely in only 11 cases, essentially in cases with positive rechallenge. Complete agreement occurred in only 6% of cases. Adding complete agreement and minor discrepancies raised the percentage to 49%.     

十二烷氮酮氟尿嘧啶凝胶治疗疣及银屑病150例

443例(男225例,女218例;年龄36±14a)皮肤病患者,其中150例(扁平疣52例、寻常疣55例、银屑病43例)外用含1.8％十二烷氮(艹卓)酮的1％氟尿嘧啶(5-FU)凝胶作为治疗组,148例外用1％5-FU凝胶及145例外用2.5％5-FU霜作为2个对照组。经双盲对照临床试验,结果表明含1.8％十二烷氮(艹卓)酮的1％5-FU凝胶的疗效明显优于2个对照组(P<0.01及P<0.005)。证明氮(艹卓)酮对5-FU确有渗透促进作用。     

Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour.

Dexenfluramine, an effective and safe serotoninergic drug with anorectic and possible food-selection-tuning properties, was investigated in a placebo-controlled study of 1 year's duration in severe and refractory obesity. The aim of the study was to assess weight loss, and changes in cardiovascular risk factors, food intake and eating behaviour. Dexfenfluramine- and placebo-treated patients achieved a similar weight loss (greater than 10% of initial weight, by 39.5 and 30.0%, greater than 20% of initial overweight by 42.1% and 32.5% and greater than 10 kg by 41.4 and 33.3%, respectively, of the initial cohorts). Furthermore, the decreases in weight (10.7 vs. 8.0 kg), in body mass index (3.9 vs. 2.9 kg m2) and in waist/hip ratio (0.04 vs. 0.02) were not significantly different. After discontinuation of the drug, the increase in weight (2.8 vs. 1.0 kg) was significantly higher in the dexfenfluramine-treated group. Except for a borderline better effect on glucose of dexfenfluramine, both groups showed similar beneficial changes in food intake and cardiovascular risk factors. Eating behaviour in response to emotional and external stimuli was comparable in the two groups, but placebo-treated patients had to restrain their eating more in order to achieve the same weight loss. Notwithstanding the fact that weight losses and an associated amelioration of health-risk factors were of similar magnitude in dexfenfluramine- and placebo-treated patients, dexfenfluramine might have a useful role in promoting a less stressed adherence to prolonged restriction of energy intake in the severe and refractory obese subject.     

Improvement of Decreased Critical Flicker Frequency (CFF) in Headache Patients With Drug Abuse After Successful Withdrawal

A considerable proportion of headache patients fulfill the criteria of "drug abuse" (definition according to the International Headache Society [IHS] criteria). These patients exhibit markedly reduced vigilance and continuous performance, as shown by the results of critical flicker frequency (CFF) analysis.
The present study deals with the question whether this impairment of vigilance and continuous performance is reversible. Forty-eight headache patients with drug abuse were investigated three times by means of CFF analysis: immediately before (A), immediately after (B), and 3 weeks after having finished (C) inpatient drug withdrawal.
Immediately after withdrawal, a significant decrease of headache intensity was observed. The CFF values, however, remained unchanged at a depressed level, probably due to withdrawal medication and the initial sedative side effects of thymoleptic agents (given as prophylaxis).
Three weeks after withdrawal, however, the CFF values were significantly improved, and were now within a range not far from the normal values known from a healthy general population. Thus, even after many years of drug abuse, headache patients have a good chance to improve their vigilance and continuous performance and to reach normal or close to normal levels.     

Investigation of Direct Causes of Drug Relapse and Abstainers’ Demands in a Compulsive Detoxification Center in Wuhan City of China

Objective To identify the direct causes of drug relapse and abstainers’ demand, and to develop programs for the prevention of drug relapse. Methods Abstainers in a Compulsive Detoxification Center in Wuhan City, capital of Hubei Province were randomly selected. An investigation on the direct causes of drug relapse and abstainers’ demands was conducted with multiple-choice questionnaires and face to face interviews. Data were analyzed with SPSS 12.0. Results The direct causes leading to drug relapse included: temptation to use drug again by themselves or by their drug mates, seeking pleasure and ecstasy from drug use, relatively well off living, mental stress, irritation, demoralization, family conflicts, unemployment, feeling distrusted by the family, lack of care and love from the family, and discrimination by others. abstainers’ demands after detoxification and returning to the society included: care and support from the family, employment assistance, changing living environment, understanding by others, support from the society, and keeping far away from drugs. Conclusions Environmental factors are the direct causes of drug relapse, and negative irritation is its predisposing causes. Leaving former residence, more care and help given by both the family and the society and raising their overall quality of life are the demands of abstainers.     

中西药合用对帕金森病大鼠旋转行为的影响

目的 观察中西药合用对帕金森病(Parkinson disease，PD)大鼠旋转行为的影响。方法 采用6羟多巴胺注射于脑右侧黑质造成偏侧帕金森病模型，并用滋补肝肾、通络解毒的中药以及西药美多巴进行治疗，同时设立美多巴对照组，观察中西药合用对PD大鼠旋转行为的影响。结果 中西药合用可使模型大鼠的旋转圈数明显减少。结论 中西药合用能明显改善PD模型大鼠的旋转行为。     

进展期霍奇金病经化疗达完全缓解后,巩固放疗的Meta分析

目的 应用Meta分析的方法评价进展期霍奇金病经化疗达完全缓解后巩固放疗的作用。材料和方法 在MEDLINE、CBMdisc数据库检索进展期霍奇金病化疗达完全缓解行巩固性放疗或不行巩固性放疗的前瞻性随机对照研究。对入选研究的总生存、无事件生存优势比进行Meta分析。结果 4项研究入选，以α=0．05为检验水准，巩固性放疗组与对照组(不作巩固性放疗)相比，5年总生存优势比=1．18，P=0．46；5年无事件生存优势比=1．05．P=0．83：巩固性侵犯野放疗组与对照组相比，5年总生存优势比=0．96，P=0．87。结论 进展期霍奇金病经化疗达到完全缓解后，巩固性放疗对总生存及无事件生存均无益处。     

EMPACT syndrome

Background: Seizure prophylaxis with phenytoin is a common measure in oncologic patients with brain metastases. In these patients, generalized severe adverse drug reactions such as erythema multiforme (EEM) may occur. However, in a subgroup of patients with brain radiation therapy, EEM‐like lesions develop particularly in the radiation field. Most recently, the acronym EMPACT ( E rythema M ultiforme associated with P henytoin A nd C ranial radiation T herapy) was proposed to specifically describe this syndrome. Patient/Method: Here, we report on EMPACT syndrome in a 46‐year‐old woman. Therapeutic measures included seizure prophylaxis with phenytoin and total brain radiation therapy of brain metastases from bronchial carcinoma. Three weeks after introduction of phenytoin, the patient presented with EEM‐like skin lesions restricted to the original radiation field and facial mucocutaneous involvement. After a few days, the rash spread to the upper part of the body. She was also in poor general condition. Results: The immediate cessation of phenytoin therapy, combined with administration of systemic corticosteroids and high dose immunoglobulins along with intensive local treatment and pain medications, resulted in complete resolution of the skin eruption. Patch testing to phenytoin was positive after 72 hours. Conclusion: EMPACT should be classified as an specific entity among the EEM‐like drug reactions as it only appears after radiotherapy and seizure prophylaxis with the anticonvulsant phenytoin. We propose including specific type IV‐sensitization to phenytoin into the definition of EMPACT.