Introduction to the pharmacoeconomics of herbal medicines.

This article explores the need to perform pharmacoeconomic evaluations of herbal medicines and assesses the extent to which this approach has been applied so far to these products. There seems to be no compelling need for pharmacoeconomic analyses of herbal over-the-counter medicines, but such analyses are certainly warranted for herbal prescription medicines that have a high level of reimbursement. Such preparations are used in Germany, in particular, where physicians prescribed ginkgo, hawthorn, St John's wort, horse-chestnut and saw palmetto to a value of more than DM50 million each in 1996. In our survey, only a single pharmacoeconomic study, of uncertain quality, was found on these 5 herbs, whereas several pharmacoeconomic reports on synthetic competitors were retrieved. The time has come to submit highly reimbursed herbal prescription medicines to the same rigorous pharmacoeconomic evaluations as their synthetic competitors. At present, such studies are particularly important for Germany, but in the future they may also become relevant for other countries, inside as well as outside Europe.

Reporting format for economic evaluation. Part II: Focus on modelling studies.

This article presents the first version of a reporting format for modelling studies which is based on a general reporting format by our taskforce, which was published in the previous issue of this journal. The use of decision-analytical models for economic evaluations is increasing because, in practice, it is not always possible to derive information from prospective studies. However, the acceptance of modelling studies is generally lower than prospective studies not only because of the use of secondary data, but also because the reports of modelling studies do not always have sufficient transparency. Hence, a standardised reporting format may improve the transparency and, consequently, the acceptance of modelling studies. This article presents an example of a reporting format for economic evaluation based on modelling studies, which may facilitate the development of future guidelines for modelling studies. The format consists of a number of headings, which are followed by a brief recommendation on the content. This format does not deal with methodology and data management, but especially addresses validation and quality assurance, which may increase the transparency of the report.

Reporting format for economic evaluation. Part I: Application to the Dutch healthcare system.

This article presents the first version of the reporting format for economic valuation that was created in 1995 by a multidisciplinary taskforce. The members of this taskforce come from a broad spectrum of backgrounds within the healthcare field and participated in the exercise voluntarily. The format presented should be understood as the preferred Dutch structure for the reporting of any study on economic evaluation. In view of the many areas of contention that exist within the field, this format only gives normative directions in those areas in which consensus exists, as evidenced by the current published international guidelines. A regular review and adaptation of this format will be needed to reflect advances in the field.

[The clinical lesson in the Nederlands Tijdschrift voor Geneeskunde in the last 40 years]. / De Klinische les in het Nederlands Tijdschrift voor Geneeskunde in de afgelopen 40 jaar.

'Lessons of the Week' have been published in Nederlands Tijdschrift voor Geneeskunde since 1928. They consist of a clinical patient demonstration on paper but with the structure and the wording appropriate for a college theater. These lessons are read by three quarters of the journal's readership. They are usually written by senior clinicians.

[What do reviewers look for in 'original articles' submitted for publication in the Nederlands Tijdschrift voor Geneeskunde?]. / Waarop letten beoordelaars van 'oorspronkelijke stukken' die ter publicatie zijn aangeboden aan het Nederlands Tijdschrift voor Geneeskunde?

OBJECTIVE: To determine to what extent reviewers of the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine, NTvG) use specific criteria when reviewing original articles. DESIGN: Descriptive. SETTING: Editorial office of the NTvG. METHODS: From 21 October 1993 to 1 March 1994, 89 original research manuscripts were received. Of these, 60 (67%) were submitted to reviewers. Each manuscript was sent to a second reviewer, with the same expertise, as well. On the basis of two checklists with a total of 16 quality elements, the manuscripts were analysed and compared with the chief editor's judgement. The results of each individual referee were correlated with his year of graduation. The duration of the peer review procedure was established. RESULTS: The reviewers of the NTvG responded to 46% of the explicit questions from the editors (list one), while they commented upon 43% of the criteria in the second implicit list. There was no relation with the year of graduation. Approximately 12% of the flaws in the manuscripts, as assessed by the editor, were missed. About 42% of the correct elements in the manuscript were not mentioned in the evaluation. The interrater agreement between paired reviewers was 0.26 (kappa); on average 10.4 of the 16 checkpoints were mentioned or not by both. Peer review took 41 days on average. CONCLUSION: Only a small fraction of the flaws in a manuscript were missed by the reviewers. Peer review is reasonably uniform at the NTvG, but would probably benefit from standardization.

The relationship between serum triiodothyronine and thyroxine concentrations in hyperthyroidism.

In toxic nodular goitre relapses of hyperthyroidism after medical therapy probably are more common than in toxic diffuse goitre. It has also been reported that in patients with toxic diffuse goitre a high ratio of triiodothyronine (T3) and thyroxine (T4), initially or during medical treatment, predicts a relapse of the hyperthyroidism after cessation of therapy. We therefore studied the relationship between T3 and T4 in untreated patients with toxic diffuse goitres (n = 46, mean ratio T3/T4 29.6 nmol/mumol +/- 10.7 SD) and toxic nodular goitres (n = 12, ratio 29.3 +/- 17.1), and found no significant difference. Both groups differ significantly from normal controls (n = 16, ratio 14.6 +/- 1.5, P < 0.01). From the patients with toxic diffuse goitres we compared two groups. Patients in the first group remained in remission after short-term medical treatment (n = 10); the second group contains patients with a relapse of hyperthyroidism (n = 10). Differences between both groups in the median ratio of T3 and T4 were assessed before the start of treatment, at 4 and at 8 weeks. No significant differences were found between the two groups. The ratio of T3 and T4 is not helpful in distinguishing diffuse and multinodular toxic goitre or in determining the prognosis after medical treatment of hyperthyroidism caused by a hyperfunctioning thyroid gland. However, recurrence of hyperthyroidism was found in 3 patients with a T3/T4 ratio > 60 nmol/mumol after 8 weeks of treatment.

[Meeting reports in the Nederlands Tijdschrift voor Geneeskunde; value for readers and associations]. / De verenigingsverslagen in het Nederlands Tijdschrift voor Geneeskunde; het nut voor lezers en verenigingen.

OBJECTIVE: To determine the objective of scientific association proceedings in the Nederlands Tijdschrift voor Geneeskunde (NTvG) and whether the objective is met by publication. DESIGN: Interview. SETTING: The editorial office of NTvG MATERIAL AND METHODS: The clinical relevancy of the proceedings published in 1990 and 1991 was determined using selection criteria. 53 (former) secretaries of scientific associations which publish their proceedings in NTvG were interviewed by written questionnaire, and 101 physicians were interviewed by telephone, asking for their opinion on the objective and the use of publishing the proceedings. RESULTS: Of the proceedings (1610 abstracts) published in 1990 and 1991 20% were considered clinically relevant. The opinion of the secretaries of the associations was that the objective of the proceedings is to record medical information and to provide a medical newspaper for the latest reports of the associations, mostly intended for all readers of the NTvG. The secretaries usually correct the abstracts with respect to form and to a lesser extent to informative value. Editorial office selection of the abstracts was not considered desirable, guidelines with regard to writing an abstract of the proceedings were appreciated. More than half of the family physicians read the proceedings, but often considered them too specialised. Half of these thought editorial office selection of the abstracts advisable. About 80% of the specialists read the proceedings, of which the informative value was considered variable. They disapproved of editorial selection. In general physicians read the proceedings very selectively. CONCLUSIONS: The clinical relevancy of the abstracts of the proceedings leaves much to be desired. The objective is to provide a medical record and a newspaper for all readers, but these read the proceedings very selectively. The informative value could be improved. Abstract selection should be in the hands of the associations' secretaries only, but guidelines from the editorial office on writing abstracts are welcomed.

[Revision consensus osteoporosis]. / Herziening consensus osteoporose.

Several years ago a consensus guideline conference was organised both in the United States (1984) and in the Netherlands (1985) on case finding, prevention and treatment of osteoporosis. The most important conclusion of both conferences was that oestrogen substitution can significantly reduce the incidence of fractures in postmenopausal women. This statement has not changed in the revised guidelines on osteoporosis of 1991. As far as the effect of hormonal substitution of oestrogens with or without progestagens in relation to cardiovascular disease and breast and endometrial carcinoma is concerned, insights have hardly changed in the last 5 years. The value of other drugs in the treatment of osteoporosis, however, has become better known. Both diphosphonates and anabolic steroids have recently made a comeback.

Logistic multiple regression analysis of factors predicting recurrence of hyperthyroidism after medical treatment of toxic diffuse goitre.

In order to determine which factors predict the outcome of short term antithyroid drug treatment we studied 42 patients with diffuse goitre in whom 43 instances of thyrotoxicosis were treated. Treatment duration ranged from 24 to 61 wk (median 30 wk). All patients received high-dose carbimazole and thyroid hormone substitution. Patients in remission were followed for 39 to 134 wk (median 73 wk). The relapse rate at 1 yr and at 2 yr after cessation of antithyroid drug treatment was 51%. Of the parameters studied presence or absence of eye signs and initial serum levels of thyroxine, triiodothyronine and immunoglobulin-G in the relapse group and in the remission group showed significant differences in univariate analysis. No significant differences were found for age, sex, family history of thyroid disease, thyroid gland volume or TSH-receptor stimulating autoantibodies. Linear discriminant analysis shows that of the four remaining factors thyroxine is not important in separating both groups. Cox analysis yields only initial serum triiodothyronine and eye signs as significant prognostic factors. With these two factors 18 out of 23 predictions of remission and 16 out of 18 predictions of relapse in the 41 patients with known initial serum triiodothyronine concentrations are correct. Such predictions can be used in the choice of therapy, short-term medical treatment for patients with a low risk and long-term medical treatment or, at the appropriate time, a destructive form of therapy for patients with a high risk of relapse.

[Reasons for rejection of articles vor publication in the Nederlands Tijdschrift voor Geneeskunde in 1990]. / Redenen van afwijzing van artikelen voor publikatie bij het Nederlands Tijdschrift voor Geneeskunde in 1990.

To deduce recommendations for authors which decrease the rejection probability we investigated retrospectively which reasons were mentioned in 1990 by the editorial board of the 'Nederlands Tijdschrift voor Geneeskunde' when it rejected original articles, reviews, clinical lessons and case reports, and whether length of the article, professional status of the first author, most relevant specialism and origin of the article influenced the rejection probability. Out of 547 articles 38% (208) were rejected; case reports were rejected most often (49%), reviews least often (33%). Peer review of original articles was the most thorough, of case studies the least. The most frequent reason for rejection in all categories was 'substantial shortcomings', particularly in the original articles (80%). Rejection of clinical lessons and case studies was relatively often due to criteria concerning the clinical message. Both rejected and accepted articles on average exceeded the length limit. Professional status and specialism were associated with a difference in rejection probability (chi 2, p less than 0.05). Specialists had the lowest rejection probability (31%). Nonspecialists benefited from specialist supervision. Articles originating from non-academic institutions were more often rejected than articles from academic centres. We advise authors to judge their articles by means of the criteria mentioned. Consultation of (methodological) experts, literature data bases, and (or) the editorial board can improve their chances. Non-specialists can benefit from the experience and expertise of specialists. In general, scientific attitude and willingness to alter the article according to editorial advice appear to have beneficial results.

[Vitamin D poisoning; real and spurious]. / Vitamine D-intoxicatie; echt en onecht.

Vitamin D in large doses is a proper therapy in hypoparathyroidism, osteomalacia, vitamin D-resistant rickets and also in chronic renal failure although in those cases the active metabolite of vitamin D is preferred because of the much shorter biologic halflife. Apart from these disorders there are no good reasons for using megadoses of vitamin D. Pseudo-vitamin D intoxication is caused by granulomatous diseases as a so-called inappropriate calcitriol secretion. In cases of vitamin D intoxication the 25-OHD3 content in the serum is much too high, the parathyroid hormone concentration is suppressed and the I,25-(OH)2D3 level is low, whereas in pseudo-vitamin D intoxication the 25-OHD3 content in the serum is normal and the I,25-(OH)2D3 is seriously elevated. Cultured alveolar macrophages of patients with sarcoidosis can produce I,25-(OH)2D3 as can sarcoid lymph node homogenate. I,25-(OH)2D3 proved to promote the fusion of alveolar macrophages to form polykaryons. Local concentrations of I,25-(OH)2D3 may be higher at sites of granulomatous tissue and can act in a paracrine or autocrine fashion to enhance granuloma formation. The action of glucocorticoids and chloroquine in patients with sarcoidosis and hypercalcaemia is presumably an interruption of the described vicious circle.