Contribution of adverse drug reaction to admission rates in an acute psychiatric ward

The relative contribution of adverse drug reactions (ADR) to the admission rate of an acute psychiatric ward was examined prospectively. Among 321 patients hospitalized over a period of 17 months, adverse drug reactions were the main cause for hospitalization in 7.5%. Extrapyramidal side effects - mainly resistant akathisia - account for half of these patients. The population at high risk was that of the elderly and those suffering from organic brain syndromes.     

Reliability of adverse drug reaction assessment in psychiatric inpatients

Summary Within an ongoing drug surveillance program in psychiatric hospitals the applicability of an algorithm for judgment on probability of causal relationship of adverse events and drug therapy was tested. Algorithmic interrater agreement was compared to agreement obtained with the conventional criteria used so far within the program in 80 cases by two raters, who had participated in the drug surveillance program since its beginning in 1979. With the use of the algorithm raters agreed on imputed drugs in 86% of all cases; total agreement on drugs and degree of probability was obtained in 69% (weighted kappa 0.618). Raters agreed on total score for the imputed medication in 49% and also on all subscores for the different axes of the algorithm in 43% of all cases.Differentiation of drug-related from illness-related changes, the use of judgmental terms within the algorithm and specific problems created by the frequent use of combinations of drugs with similar profiles of adverse drug reactions (ADR) in psychiatric patients were identified as the main sources of disagreement. Agreement on total judgment was comparable to results from similar studies in the literature using various algorithms, but in contrast to all these studies a higher percent of agreement (80%) was obtained with the use of the conventional criteria in this study.     

氯氟(艹卓)乙酯治疗焦虑障碍的不良反应

目的观察氯氟(艹卓)乙酯治疗焦虑障碍的不良反应.方法采用双盲双模拟、多中心、随机、平行对照研究.共观察患者163例,其中试验组(氯氟(艹卓)乙酯组)82例,对照组(地西泮组)81例.试验组早、午餐后同时服用一片氯氟(艹卓)乙酯安慰剂片衣一片地西泮安慰剂片,晚餐后同时服用一片氯氟(艹卓)乙酯片2 mg及一片地西泮安慰剂片;对照组早、午、晚餐后同时服用一片氯氟(艹卓)乙酯安慰剂片及一片地西泮片2.5 mg,疗程为4 wk. 结果治疗4 wk后,试验组出现至少1项不良反应的病例数为25例,总的不良反应发生率为30.5%,可能与药物有关的病例数为10例,主要的不良反应为头昏、困倦、厌食、口干等;对照组出现至少1项不良反应的病例数为27例,总的不良反应发生率为33.3%,可能与药物有关的病例数为7例,主要的不良反应为头昏、困倦、衰弱、口干等. 结论氯氟(艹卓)乙酯治疗焦虑障碍有明显疗效,无明显不良反应.     

Adverse drug reactions to dopamine agonists: A comparative study in the french pharmacovigilance database

Pharmacodynamical differences between dopamine agonists (DAs) suggest differences in their adverse drug reactions (ADRs) profile. In this study, frequencies of ADR to DAs or levodopa reports in the French Pharmacovigilance Database were explored. Reports occurring between January 1, 1984 and December 31, 2008 were selected (2,189 for DAs and 1,315 for levodopa). The numbers of ADRs by system organ class were compared using ropinirole as a reference. Diurnal somnolence was less frequently reported with all DAs when compared with ropinirole (P < 0.001). Impulse control disorders (ICDs) were more frequently reported with pramipexole (P < 0.001). Significant difference was found among DAs in the frequency of confusion or disorientation (P < 0.001), nausea and vomiting (P < 0.05), or edemas (P < 0.001). No difference among DAs was observed in the frequency of hallucination or arterial hypotension ADR reports (P = 0.3 and P = 0.1). Pleural effusions were more frequently reported with pergolide or bromocriptine (P < 0.001). Somnolence or ICD reports were less frequent with levodopa, whereas confusion was more frequently reported. In summary, our data show significant differences in the kind of ADRs reported for each DA. © 2010 Movement Disorder Society.     

Difficulties in assessing adverse drug reactions in clinical trials

1. The discovery of an adverse drug reaction (ADR) depends on: the relative frequencies of the drug-related and non-drug events; the mechanism of drug-induced toxicity; the number of patients exposed to the drug; and the methods used for detecting toxicity. Clinical trials are usually short-term studies conducted in a few hundred patients before marketing a drug. Therefore only the most common acute, dose-related ADRs are usually detected in the pre-marketing phase. 2. The detection and assessment of ADRs in clinical trials is still inadequate. Unstructured (open-ended questionnaires) and structured procedures (checklists) are the methods most commonly used. Since both methods have limitations, the discovery of ADRs in pre-marketing trials (phases I to III) should also rely on the complementary information provided by other methods: physiological and physical examinations, and pertinent laboratory tests. A more definite assessment of individual cases of ADRs should include the use of the adverse drug reaction probability scale (APS) or similar procedures. 3. Because the knowledge on the clinical toxicity of a drug will always be incomplete at the time of marketing, further investigation of the frequency and determinants of ADRs must be pursued in the post-marketing phase.     

An epidemiological study of minor psychiatric disturbances

Summary A representative epidemiological field study of minor mental disturbances among 19- to 20-year-old persons in Zurich (Switzerland) is reported. Respondents had completed two selfreport inventories; SCL-90R by Derogatis and a Syndrome List concerning psychosomatic and neurotic syndromes. There is a high prevalence rate of such disturbances. Usually, however, they do not lead to treatment-seeking behaviour. Females show higher prevalence figures on nearly all scales and syndromes. The syndromes of anxiety and depression are most prominent among females. Unexpectedly, there are few differences in prevalence rates between different socio-demographic groups. There are, however, three high-risk groups: (1) persons without occupational training; (2) persons without religious affiliation and (3) persons whose parents or siblings had psychiatric problems. Reasons for the lack of clearcut associations between social status and psychiatric syndromes are discussed.This research is supported by the Swiss National Science Foundation, grant no. 3.804-0.76.     

Idiosyncratic adverse reactions to antiepileptic drugs

Idiosyncratic drug reactions may be defined as adverse effects that cannot be explained by the known mechanisms of action of the offending agent, do not occur at any dose in most patients, and develop mostly unpredictably in susceptible individuals only. These reactions are generally thought to account for up to 10% of all adverse drug reactions, but their frequency may be higher depending on the definition adopted. Idiosyncratic reactions are a major source of concern because they encompass most life-threatening effects of antiepileptic drugs (AEDs), as well as many other reactions requiring discontinuation of treatment. Based on the underlying mechanisms, idiosyncratic reactions can be differentiated into (1) immune-mediated hypersensitivity reactions, which may range from benign skin rashes to serious conditions such as drug-related rash with eosinophilia and systemic symptoms; (2) reactions involving unusual nonimmune-mediated individual susceptibility, often related to abnormal production or defective detoxification of reactive cytotoxic metabolites (as in valproate-induced liver toxicity); and (3) off-target pharmacology, whereby a drug interacts directly with a system other than that for which it is intended, an example being some types of AED-induced dyskinesias. Although no AED is free from the potential of inducing idiosyncratic reactions, the magnitude of risk and the most common manifestations vary from one drug to another, a consideration that impacts on treatment choices. Serious consequences of idiosyncratic reactions can be minimized by knowledge of risk factors, avoidance of specific AEDs in subpopulations at risk, cautious dose titration, and careful monitoring of clinical response.     

A Norwegian psychiatric epidemiological study.

OBJECTIVE: This study reports results of a large-scale epidemiological investigation of the prevalence of mental disorder in Oslo. METHOD: A random sample of Oslo residents age 18-65 years was drawn from the Norwegian National Population Register. A total of 2,066 subjects, 57.5% of the original sample, were interviewed with the Composite International Diagnostic Interview in 1994-1997. The mean age of the interviewed subjects was 39.3 years. RESULTS: The 12-month prevalence of all mental disorders was 32.8%, and the lifetime prevalence was 52.4%. Alcohol abuse/dependence and major depression had the highest lifetime prevalence and 12-month prevalences. All mental disorders were more prevalent in women than in men, with the exception of alcohol and drug abuse/dependence. Severe psychopathology (e.g., three or more diagnoses) was found in 14%-15% of the respondents. The lifetime and 12-month prevalences for all diagnostic categories except drug abuse/dependence were similar to those found in the United States Comorbidity Survey. CONCLUSIONS: Epidemiological data for Oslo show that the lifetime and 12-month prevalences of mental disorder are quite high, with alcohol abuse/dependence and major depression particularly frequent. The rates for women are higher than those for men for all diagnostic categories, except for alcohol and drug abuse/dependence.     

An epidemiological study of the clinical impact of pharmacokinetic anticonvulsant drug interactions based on serum drug level analysis

The impact of pharmacokinetic anticonvulsant drug interactions on prescribing patterns and serum drug level distribution in a routine clinical setting was evaluated in a population of 848 patients chronically treated with phenytoin, phenobarbital, carbamazepine and valproic acid (either alone or as two-drug combinations) and referred for therapeutic drug monitoring for the first time. While dosages of each drug did not differ significantly between monotherapy and polytherapy patients, significant differences in serum level distribution were found. The proportion of patients with suboptimal serum carbamazepine and valproic acid levels (<4 and <50μg/ml, respectively) was much greater in the polytherapy than in the monotherapy groups, probably as a consequence of induction of carbamazepine and valproic acid metabolism by combined anticonvulsants. Conversely, the proportion of phenobarbital levels above the upper limit of the optimal range (40μg/ml) was greater among patients receiving phenytoin in combination than among patients taking phenobarbital alone, presumably as a result of phenytoin-induced inhibition of barbiturate metabolism. The therapeutic implications of these findings are discussed.

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Sommario Il presente studio è stato condotto al fine di valutare, in condizioni cliniche rutinarie, i possibili effetti delle interazioni farmacocinetiche degli anticonvulsivanti su: (I) le prescrizioni delle dosi giornaliere e (II) la variabilità dei livelli plasmatici dei singoli farmaci. La casistica comprende 848 pazienti epilettici sottoposti, per la prima volta ad un dosaggio ematico e trattati cronicamente con uno o due dei seguenti farmaci: fenitoina (PHT), fenobarbital (PB), carbamazepina (CBZ) e valproato (VPA). Nessuna differenza significativa è stata osservata nelle prescrizioni delle dosi giornaliere tra i gruppi in monoterapia e quelli in biterapia. Per quanto riguarda la variabilità dei livelli ematici, sono state osservate le seguenti differenze statisticamente significative: (I) una più alta percentuale di pazienti con livelli di CBE e VPA al di sotto dei ?ranges? tereapeutici nei gruppi che assumevano tali farmaci in associazione con uno degli altri considerati, rispetto ai gruppi in monoterapia; (II) una percentuale più alta di pazienti con livelli di PB al di sopra del ?range? nel gruppo trattato con PB e PHT in associazione, rispetto agli altri gruppi considerati. Le implicazioni cliniche di tali dati vengono, quindi, discusse.

     

An epidemiological study of brain tumours in the elderly

Abstract

An epidemiological study of brain tumours in elderly Japanese was undertaken on the basis of a report from the All Japan Brain Tumor Registry. Thus, the recent status of brain tumours in elderly Japanese could be clarified. Accordingly, the formerly compiled characteristics of brain tumours in the elderly should more or less be revised. However, we are all still facing the same unfavourable prognosis of brain tumours in the elderly as before.     

Guillain-Barré syndrome in Cantabria, Spain. An epidemiological and clinical study

Seventy-one patients with Guillain-Barré syndrome (GBS) were retrospectively selected from within a defined area (Cantabria) in northern Spain, from 1975 to 1988. Excluding two non-resident cases, epidemiological analysis was based on 69 cases. The annual incidence rates were stable during the 14-year period of study with an average incidence of 0.95 (age-adjusted, 0.86) cases per 100000 population. No significant difference was found for sex, urban or rural residence and there was no significant seasonal clustering. Antecedent event were recorded in 57% of patients, the most frequent events being upper respiratory infection and gastroenteritis. No association between use of gangliosides and the syndrome was found. Eight patients had variant syndromes including Fisher's syndrome (2 cases), and axonal (4 cases) and sensory (2 cases) GBS. Recurrences occurred in 3 cases. Excluding nine patients with incomplete follow-up and two with Fisher's syndrome, clinical analysis was based on 60 cases. Patients were divided into three groups as a function of their peak weakness. Significant features of the severe group were a requirement for ventilation, presence of bulbar palsy or dysautonomia and a longer duration of the plateau phase. However, it was not possible at an early stage of the clinical course to predict future motor deficit. Four (6.7%) patients belonging to the severe group died during the acute phase of the disease. No specific treatment for GBS was given. Outcome was assessed by means of serial examination up to 24 months after the onset of symptoms using a functional scale. At 3, 6 and 24 months 70%, 46% and 12% of patients, respectively, had a poor outcome. Features associated with poor outcome at three months include speed of progression, duration of the plateau phase, age greater than 40 years, severe weakness at the nadir, presence of denervation and a small or absent compound muscle action potential of the median nerve.     

Hosts to adversity. I. An epidemiological perspective

A community sample of 574 women provided information on their experience of life events during a 6-month period. Events were classified according both to their severity and their dependence (the extent to which each respondent was rated responsible for event occurrence). This report presents results based on an analysis of the relationship between event rates and psychosocial factors, the psychosocial determinants of the prevalence of Research Diagnostic Criteria diagnoses, and the extent to which knowledge of case and social factor status (statistically) accounted for event rate.     

An epidemiological study of mental health and socioeconomic conditions in Sumatera, Indonesia.

A mental health survey was conducted in Palembang, Indonesia, to test the hypothesis that rapid socioeconomic and cultural change is detrimental to mental health. The 30-item General Health Questionnaire, translated into Bahasa Indonesia, was administered to a probability sample of 1670 adults (94.9% of the target sample). The Present State Examination was conducted on a weighted subsample of 100, using a 2-phase design. Overall morbidity rates were surprisingly similar to those in industrialized countries. A strong association was found between psychological symptoms and poverty. Persons belonging to communities that had progressed substantially in standards of living had fewer symptoms. The evidence points to a possibly beneficial effect of economic progress on mental health. Longitudinal data are needed to confirm this.     

An epidemiological study of multiple sclerosis in central Sardinia, Italy

Objectives – To verify morbidity estimates in central Sardinia, Italy. Methods – A prevalence study was performed in the province of Nuoro, Central Sardinia, which has a population of 273,768 inhabitants (135,383 men and 138,385 women). A complete enumeration approach was adopted by using all possible case-collection sources. Results – On prevalence day, December 31, 1993, 394 subjects (124 men and 270 women) living in the study area were known to suffer from definite and probable MS, giving a crude prevalence rate of 143.9 cases per 100,000 people, 91.6 for males and 195.11 for females. The crude prevalence estimated on December 31, 1985, based on 282 MS cases alive in the study area, was 102.94 per 100,000. Conclusion – This study reinforced central Sardinia's position as a high and rising prevalence area for MS.     

Sex difference in prevalence of minor psychiatric morbidity: a social epidemiological study in Taiwan

The female excess in prevalence of minor psychiatric morbidity (MPM) evident in a community study in Taiwan (n = 1023) was further investigated in terms of demographic variables, socioenvironmental risk factors and psychosocial stresses. It was suggested that a stronger effect of chronic psychosocial stressors accounted for the higher prevalence of MPM in women. Further analysis has revealed a longer mean duration of MPM in women and an incidence ratio close to unity between the sexes. These retrospective findings were further examined in a small one-year prospective outcome study; a poorer outcome was found among older subjects and female subjects. It is suggested that more females have MPM because chronic psychosocial stressors more adversely affect the course of such morbidity. These results are discussed in a cross-cultural context.