Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case-control studies and evidence of publication bias.

We investigated the association of the dopamine D2 receptor (DRD2) Taq1A polymorphism and alcoholism, using meta-analytic techniques, and specifically undertook an investigation of possible publication bias. Potential publication bias represents a genuine risk to the integrity of published research, but its impact has rarely been documented. We observed a small effect of the DRD2 Taq1A polymorphism on risk of alcoholism, indicating increased alcoholism in individuals possessing the A1 allele of the Taq1A polymorphism (OR=1.21, 95% CI 1.13-1.30, P<0.001). This association remained significant when data from samples of European and East Asian ancestry were analyzed separately. We did not find evidence for association in high-severity alcoholism compared to low-severity alcoholism. Removing the first published study significantly reduced the magnitude of the pooled effect size estimate, although the association remained significant. In addition, we observed evidence for possible publication bias and for the strength of individual study effect size to be inversely related to year of publication. These results support the association of the DRD2 Taq1A polymorphism with alcoholism. This conclusion is qualified by the possibility of publication bias in the literature and the observed between-study heterogeneity, which indicates that the observed association may differ in strength between populations or may not exist at all in some populations.

Structuring prescribing data into traffic-light categories; a tool for evaluating treatment quality in primary care.

BACKGROUND: Prescribing feedback based on aggregated data alone does not give the information needed to improve treatment quality. OBJECTIVES: Our aim was to develop a new method, or tool, of presenting prescribing feedback which, combined with guideline recommendations, makes it possible for doctors to judge their own prescribing as good or bad. METHODS: Asthma was chosen as a disease model, as treatment recommendations are readily available published as national and international guidelines. Four mean daily dosage intervals of inhaled short-acting beta-agonists and four mean daily dosage intervals of inhaled steroids were combined into a 4 x 4 matrix. This matrix of 16 combined dosage boxes was presented to 68 Norwegian GPs participating in peer review groups. As a first step, the GPs in the groups reached consensus on what they considered to be appropriate and inappropriate combined dosage intervals of these drugs based on national guideline recommendations and their joint clinical experience. Accordingly, traffic-light colours, green and red, were assigned to the combined dosage boxes in the matrix. Treatments in boxes difficult to judge were coloured yellow. During a 1-year period prior to the consensus meetings, the dispensed inhaled short-acting beta-agonists and inhaled steroids of each of the doctors' patients were recorded at the local pharmacies. As a second step in developing the new method, the number of patients treated within each of the coloured boxes was presented to the GPs in the peer review groups. These combined presentations provided an overview to the whole group, and individually to each GP, of how many patients were actually given appropriate or inappropriate treatment according to their own agreed upon standard. RESULTS: The GPs categorized 34% of 1122 evaluated patients receiving inhaled short-acting beta-agonists or inhaled steroids as treated inappropriately during the 1-year registration period. Appropriate treatment was given to 47% of the patients, and in 19% of the cases the treatment was difficult to evaluate. CONCLUSIONS: A method has been developed enabling GPs to categorize prescribing information into good (green), bad (red) and difficult to judge (yellow) treatment qualities, based on guideline recommendations and clinical experience. The actual prescribing data for each GP were labelled according to the same colour scheme, thus revealing to each GP his or her own actual prescribing compared with their own treatment standard, yielding information and motivation for quality improvement efforts.

Promoting breastfeeding in rural Gambia: combining traditional and modern knowledge.

Sub-optimal breastfeeding practices still prevail in many countries, especially in traditional rural communities. Despite high breastfeeding initiation rates and long total duration of breastfeeding, exclusive breastfeeding is a rare practice. In the present study, quantitative methods were used to identify current infant feeding practices in 12 rural communities in The GAMBIA: Results indicated that delayed initiation of breastfeeding, prelacteal feeding and failure to practice exclusive breastfeeding were widespread. Qualitative data further indicated that current beliefs and practices were strongly influenced by traditional beliefs and practices. These were kept very much alive by elders, both women and men, including husbands. The results also showed an unexpected support for bottle-feeding from both male and female elders who considered it part of the modernization process. A strategy for promoting early initiation of breastfeeding, feeding of colostrum and exclusive breastfeeding for 6 months in rural communities should therefore incorporate traditional beliefs and practices into modern messages on optimal breastfeeding. Traditional beliefs and practices in the study setting that could be used in this way included knowledge from the population's acquaintance with the newborns of their livestock. It also included the traditional practice of mothers taking their very young children with them when going to work in the fields. The paper suggests such a strategy by developing a matrix to establish linkages between modern and traditional knowledge on a specific practice. Such linkages facilitate the acceptance of recommendations on infant feeding by mothers in these communities. The strategy recommends an expanded target group to include elders and husbands, as the data show that these groups are highly influential in matters regarding patterns of child feeding.

[Should pethidine still be administered to women in labor?]. / Skal vi fortsatt gi petidin til fødende?

According to surveys from 1988, 1992 and 1996, Norwegian obstetric departments are still to a large extent using pethidine as birth analgesia. In this article we report recent knowledge of various pharmacological effects of pethidine in mothers and newborns. Pethidine has mainly a sedative effect, but very little analgesic effect in parturients. Pethidine has relatively long-acting behavioural and neurological effects in the newborn due to slow elimination. As a result, breastfeeding is delayed and the mother-infant interaction is disturbed according to recent studies. There is concern about the more or less routine administration of pethidine in many hospitals. We conclude that obstetric departments should reconsider their use of pethidine.

The doctor-patient relationship and the management of asthma.

General practitioners (GP) differ in views on how to relate to their patients, diagnose asthma and update their knowledge. By understanding the doctors' attitudes within these domains it is possible to design a better information strategy and improve disease management. In order to get insight in the doctors' experiences and ways of thinking regarding asthma, 20 GPs were interviewed. A phenomenographic analysis was applied in describing the doctors' opinions. The doctors' opinions about who was in charge of the asthma management defined four doctor-patient relationships: I will manage it, you will manage it, we will manage it and I do not know whether I will manage it. The GPs differed markedly in how much they trusted the patients' descriptions and the physiological measurements of the disease. Three opinions on how to acquire knowledge were described. Knowledge should be acquired either from experts or from peers. Another belief did not give weight to a defined source but expressed the necessity of using all opportunities at hand. Doctors holding this belief, "the bricoleurs", seemed to be more interested in a "how to do it" than a "why to do it" information. We conclude that strategies for improving asthma management should consider the importance of both patients' accounts and physiological measures, the degree of co-operation between doctors and their patients and eventually the ways and styles of acquiring new knowledge about asthma.

[Antidepressive agents and breast feeding]. / Antidepressiver og amming.

Postpartum blues occurs in 50-80% of women. A few percent of the cases are classified as serious postpartum depression, requiring antidepressant treatment. There is a growing understanding that women should continue to breast-feed in this situation. Data concerning the transfer of antidepressants into breast milk has been researched. Calculations of the infant relative dose via breast milk were done for the drugs concerned. Few antidepressants have been studied at steady state conditions in nursing mothers. Nortriptyline and amitriptyline have minimal relative doses and can be used when breast-feeding. Doxepine should be avoided, as should lithium, which has a significant transfer. Among the serotonine-reuptake inhibitors fluoxetine has been well studied in breast milk. Since fluoxetine has a long half life and a high transfer, sertraline and possibly paroxetine are better alternatives, but the latter has not yet been studied in repeated doses. Moclobemide also lacks data from multiple dose studies, but extrapolation to steady state indicates that the relative dose is small. More observational studies should be carried out in infants breast-fed by mothers using antidepressants. In the meantime, doctors prescribing antidepressant drugs to nursing mothers should see that the infants are monitored for side effects.

Direct mailing of consensus recommendations did not alter GPs' knowledge and prescription of oestrogen in the menopause.

OBJECTIVE: To investigate the impact of an information-package (direct mailing) concerning oestrogen therapy, deriving from a consensus conference in 1990, on general practitioners' (GPs') attitudes and knowledge. DESIGN AND SUBJECTS: Controlled randomised study. Two groups of Norwegian GPs. The Intervention group received an information-package consisting of the recommendations from the consensus conference, some headline questions with answers, and a classification of the oestrogens available in Norway, including a table and a graphical presentation of the costs of the different treatments. GPs stated their views on prescribing oestrogen on a five step scale, related to nine short case histories, each containing cues on complaints, smoking, family history suggesting risk for cardiovascular disease, and osteoporosis. MAIN OUTCOME MEASURES: GPs' views on prescribing oestrogen, relation to age, sex, practice type (solo/group) and practice location. RESULTS: The differences in answer distributions between the Intervention (n = 193) and Control (n = 181) groups did not reach statistical significance for any of the nine case histories. The answers indicate a more liberal attitude towards replacement therapy in 1992 compared to a study performed in 1990. The views on contraindications was fundamentally unaltered. CONCLUSION: The study did not reveal any significant effect of direct mailing as means of disseminating consensus conference recommendations to GPs.

[High-dose therapy with cytostatic agents as primary treatment of advanced breast cancer]. / Høydosebehandling med cytostatika som primaer behandling ved brystkreft med fjernspredning.

Thousands of women with breast cancer have received high dose chemotherapy prior to the results from controlled clinical trials being known. As one of these patients the author reviews and discusses the results of the first randomised study from South Africa. High dose therapy with autologous stem cell support was compared with conventional chemotherapy in 90 young women with metastatic aggressive breast cancer. Though survival was short in both groups the disease free survival was doubled in the high dose group. A significant increase was found in response rate, duration of response and survival. Data from America show the cost effectiveness of this treatment to be comparable to that of other life-saving therapies. A comparison is made with the absolute and relative survival benefit of simvastatin treatment. A Norwegian White Paper on high dose therapy does not include advanced breast cancer in the planned trial protocols. It is argued that future health planning should give high priority to the treatment of advanced breast cancer in young women.

[Is drug use in maternity wards baby-friendly enough?]. / Er medikamentbruken ved føde- og barselavdelingene mor-barn-vennlig nok?

Quality assurance in the care of breast-feeding women and their nursing infants also applies to drugs administered during delivery and puerperium. Large variations among hospitals may indicate that drug use is irrational. A survey comparing the extent of drug sales from the hospital pharmacy to maternity wards in eight Norwegian hospitals was performed in 1992 and the results were compared with data from 1988. The purpose was to examine whether the drug use was "baby-friendly" with regard to the following criteria; proven efficacy for the indication; no effect on milk ejection, milk production and interaction with infant; minimal transfer of drug to milk. Large variations were found among hospitals in the case of some oxytocic drugs. High use of oxytocin as nasal spray and metylergometrine as tablets may indicate unnecessary use of drugs. A large decrease (89%) in the use of hypnotics was found from 1988 to 1992, which may indicate previous irrational use of these drugs. Pethidine as pain relief during delivery remained stable during this period, and was received by 40-60% of women giving birth. None of the drugs given to the mothers was assessed to represent a risk to the breast-fed infant. In general, drug use in maternity wards had decreased during the last four years and, with some exceptions, appeared to be more baby-friendly.

[Antipsychotic agents and pregnant women. A case report]. / Antipsykotika og gravide. En kasuistikk.

Teratogenic effects of drugs are not limited to visual malformations but also include developmental disturbances. Probably drugs that inhibit nerve signals such as dopamine in the central nervous system can affect the maturing of the foetal brain in the last trimester and in the postpartum period, as shown in animal studies. We have observed an infant girl with psychomotoric disturbances which occurred at the age of two weeks. The mother had received 108 mg perfenazin decanoate intramuscular injections four times during the second and third trimester, the last two times were three weeks and two days before delivery, which was at term. The symptoms resembled tardive dyskinesia. Periodically the baby showed restlessness and uttered high-pitched cries. The literature on neuroleptics indicates no major teratogenic risk, but possible risk of behavioural teratogenicity. We recommend greater caution in connection with prescribing neuroleptics in pregnancy.

[Infantile colic--what will help?]. / Spedbarnskolikk--hva hjelper?

Infantile colic occurs in 1/3 of all infants and is still a medical mystery. This paper reviews the etiology and the documented therapies. The overall aim is to avoid that inefficient forms of medication are used for this indication. It is not yet known whether colic is a dysfunction related to physical pain or behaviour. The results from 885 infants born in Oslo suggested that colic was frequent among those whose mothers both breastfed them and smoked more than five cigarettes daily. No increase in relative risk was found for other maternal or demographic factors. Since it is impossible to treat the causes parents should be advised to try general and specific strategies. General advice includes support, interest and care from health personnel and assistance from relatives. Specifically, some infants respond to either dietary changes (no cow's milk), oral sucrose infusion, vibro-accustic treatment, behavioural therapy or carrying, but avoiding hyperstimulation. Nicotine-free breast milk has not been evaluated. The available pharmacotherapy is not efficacious. Alternative medicine (herbal teas, chiropractic, acupuncture), has not yet been proven to be efficacious.

[Control of prescriptions of B-preparations. A registry study of B-preparations in Oslo and Akershus]. / Tilsyn med B-preparatforskrivningen. En registreringsundersøkelse av B-preparater i Oslo og Akershus.

In two Norwegian counties all prescriptions for benzodiazepines and analgesics containing codeine were registered over a two month period and the records were subsequently transferred to a database. 93,000 prescriptions were registered, equivalent to this 2.8 millions DDD. The registration showed great variation, both in the doctors' volume of prescribing and their prescribing patterns. 30 doctors of the total of 4,000 were responsible for 13% of the total volume prescribed. We propose that the doctors with unacceptable prescribing rates should be offered a special education program provided by the Norwegian Medical Association. The computer routines of the pharmacies appear to be inadequate for registration and research purposes. In 2% of all the prescriptions the doctors name could not be identified. Thus it seems warranted to use the doctors' identity number on prescriptions for these drugs. A reduction of the number of tablets in the largest packages dispensed should be considered by the authorities. For effective quality control of prescribing, better understanding is needed of the differences in doctors' prescribing patterns.

Excretion of psychoactive drugs into breast milk. Pharmacokinetic principles and recommendations.

The postpartum period is a time of great physical and emotional changes. The incidence of psychiatric illness is higher in this period than at any other time in a women's life. Therefore, the question of whether women receiving psychotropic drugs should continue breast feeding is an important one. Drug excretion in breast milk depends mostly on passive diffusion of the unionised unbound drug. Passive diffusion is affected mainly by the drug disposition in lactating mothers, by the physicochemical properties of the molecule and by the protein and lipid contents of breast milk. Indeed, breast milk can be considered as a compartment with bidirectional transfer rather than a reservoir into which drug accumulates. Benzodiazepines are the most prescribed psychotropic drugs. Generally there does not seem to be any contraindication to breast feeding after a single dose, provided the dose administered is relatively low. If higher doses are to be used or long term administration is required, then breast feeding should probably be discontinued, particularly with drugs with a long elimination half-life. On the basis of the average concentration of phenobarbital (phenobarbitone) in milk, breast feeding is not recommended. For glutethimide, breast feeding would appear to be safe for the infant when a single dose is taken occasionally. Zopiclone may also be prescribed on a short term basis to breast feeding mothers. Due to limited available data or to the large amount transferred to milk, administration of phenothiazines and nonphenothiazine tricyclic, butyrophenone, and benzamide antipsychotics to breast feeding mothers cannot be recommended. Breast feeding is not always considered an absolute contraindication to lithium therapy, but the mother should watch for signs of toxicity in her baby. Whether clomipramine should be contraindicated during breast feeding depends on the concentration of active metabolites in breast milk, and this has not yet been determined. It is probably safe for mothers to breast feed while receiving amitriptyline, but before more conclusive recommendations are made more infants should be studied. The available data suggest that the amount of doxepin and its metabolite in breast milk is small. However, the metabolite of doxepin may accumulate in the infant with risk of sedation and respiratory depression: therefore, an alternative antidepressant should be selected for breast feeding mothers.(ABSTRACT TRUNCATED AT 400 WORDS)