[Informed consent. A myth--or a strait-jacket for policy control?].
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Biomedical subjects
Publications and source records attributed to P K Lunde.
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Although fever is a common symptom, few studies have broadly addressed this as a clinical problem in general practice. The aims of this study were to determine the frequency of fever among general practice patients in two rural municipalities in Norway, the diagnoses (according to ICHPPC-2-def.) of conditions causing fever, and the receptionist's role in the management of these problems. All the general practitioners and their receptionists within the study area participated. During 4 weeks throughout 1988 all individuals attending their general practitioner had their body temperature measured with an electronic thermometer (orally > or = 7 years, rectally < 7 years). Fever was defined as an oral body temperature > or = 37.5 degrees C (rectally > or = 38.0 degrees C in those < 7 years). All telephone applications, including telephone encounters for fever, were recorded. Fever was detected in 80 (5%) of a total of 1610 direct encounters: 36% of those below 7 years of age (n = 70) were febrile. One-third of the total encounters for fever were telephone encounters (n = 36), of which 30% were managed by the receptionists. A wide range of diagnoses were made, most of which were associated with infectious diseases. The distribution of the diagnoses of primary care patients with fever is different from those admitted to hospital for fever of unknown origin. General practitioners and their receptionists should consider fever a diagnostic challenge, especially when the patient is handled over the telephone.
A sample of 80 direct and 36 telephone encounters for fever was established in 1988 as part of a Norwegian study on fever as a clinical problem in general practice. Reasons for encounter (ICPC) and clinical examinations were recorded along with clinical laboratory tests, treatment, management and follow up (IC-Process-PC). The doctors assessed the diagnostic process by means of visual analogue scale. Duration of the fever conditions was estimated through a postal questionnaire. Patients with direct encounters presented a wide range of reasons for the encounters. Fever was the most frequent single presenting complaint (31%). The general practitioners put major emphasis on the clinical examinations. They prescribed drugs in 68% of the direct encounters. Seventy per cent of the prescriptions were general systemic anti-infectives. Penicillin accounted for 58% of antibiotics. Six (8%) patients were hospitalized, and three (4%) were referred to a specialist. The mean time until complete recovery was 15 days for direct and 19 days for telephone encounters. Fever may be a sign even when it is not a presenting complaint. Major emphasis is probably put on the clinical examination of febrile patients because of the complexity of symptoms and the wide range of diagnoses associated with fever.
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Based mainly on economic, administrative and drug logistics indicators, the article critically reviews the use of drugs in less developed countries in the context of the global drug scene. The lack of balance in less developed countries (LDCs) between indicators of need and determinants of political, economic, professional, educational and sociocultural nature, including product marketing efforts is highlighted. Special emphasis is given to the global WHO Action Programme on Essential Drugs, its background, strategies, implementation and tentative impacts. Country case examples from Sri Lanka, Bangladesh, Kenya, Zimbabwe and the Gambia are used for illustration. Varying progress is made in about half the 110 LDCs which have formally adopted the WHO concepts. Delayed implementation, setbacks and failures are prevalent. These reflect financial and other resource constraints, political ambiguity, qualitative and quantitative deficiencies related to manpower and insufficient back-up measures of an educational and informative character. An orientation towards operational research based on competence-building according to needs and strategies is highly desirable. Accordingly a plea is made for multidisciplinary collaboration in North-South networks at university level.
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A group of senior European clinical pharmacologists presents a position paper on the possible role of clinical pharmacology (CP) in bridging the gap between academic drug evaluation and drug prescribing in primary health care (PHC). As a teaching, research and service discipline CP has developed in academic or other major hospitals while 80% of all drugs are prescribed in PHC. CP therefore has to extend its functions to PHC. Examples are given of how joint ventures between clinical pharmacologists and PHC physicians may improve the quality of drug research and increase the clinical relevance of drug information in PHC, thereby contributing towards rational drug utilization in PHC. Colleagues in PHC are invited to respond to this call for collaboration.
In a retrospective questionnaire survey of 885 women who had given birth 3-5 months before, fewer of those who were still breast-feeding at 4 months (n = 645) were using drugs than those who had stopped breast-feeding before 4 months (n = 240), during the 2 week period preceding registration. The average number of doses (Defined Daily Doses/1000 women/day) was 166 and 307, respectively, in that period. The number of doses taken was significantly associated with the use of oral contraceptive agents (p less than 0.005) and young maternal age (p less than 0.05). Most of the variation in drug use between breast-feeding and not breast-feeding mothers was probably due to the greater use of contraception by the latter. The number of drugs used per mother in the 4 month period seemed to be best predicted by her and her infant's disorders. Long-term medication in breast-feeding women included many drugs for which there is incomplete or no data about milk transfer, e.g. salbutamol, clemastine, dexchlorpheniramine, phenylpropanolamine, cromoglycate and levomepromazine. The disorders most extensively treated with drugs in this period were dyspepsia, haemorrhoids and inflammation of the breast. The finding that smoking was associated with early weaning and consumption of alcohol with prolonged breast-feeding calls for further investigation. More information on these drug and health issues to the breast-feeding mother is highly desirable.
1. In a randomized study of 22 patients in a maternity ward, the residual concentrations of two hypnotics, midazolam 15 mg p.o. and nitrazepam 5 mg p.o., in early breast milk and plasma were measured 7 h after intake on day 2 to day 6 postpartum. Milk pH, milk fat and binding to plasma proteins were also investigated. Sleep variables were scored on questionnaires. 2. No measurable (less than 10 nmol l-1) concentrations of drug in milk were found in the group receiving 15 mg midazolam at night, either after the first night or after the fifth night. Additional investigations in two mothers demonstrated that midazolam and its hydroxymetabolite disappeared rapidly from milk with undetectable levels after 4 h. The mean (s.d.) milk to plasma ratio for midazolam was 0.15 (0.06) in six paired samples. It may be assumed that practically no midazolam is transferred via early milk to the baby if the baby is nursed more than 4 h after tablet intake. 3. Milk nitrazepam concentrations increased significantly from the first (30 nmol l-1) to the fifth morning (48 nmol l-1) in the group receiving 5 mg nitrazepam at night. The mean (s.d.) milk to plasma ratio of nitrazepam after 7 h was 0.27 (0.06) in 32 paired samples, and did not vary from day 1 to day 5. Plasma protein binding of nitrazepam in puerperal women was found to be lower than that in plasma of healthy controls. The average amount of nitrazepam received by the breast-fed baby in the morning was calculated to increase from 1 to 1.5 micrograms 100 ml-1 breast milk, from days 1 to 5. In the mothers nitrazepam was associated with better hypnotic effect, but a higher incidence of complaints than midazolam. 4. Milk pH, assuming anaerobic conditions, was found in 10 women to average 6.91 +/- 0.09 (s.d.) on days 2-6 postpartum, which is less than previously reported. 5. It is concluded that both hypnotics may be used safely for a few days in the maternity ward. However, possible long-term effects in the suckling infant of small doses of benzodiazepines ingested with breast milk remain to be investigated.
The suction blister technique was used for pharmacokinetic studies with sulfonamides and trimethoprim. Blisters produced by suction (-0.3 kg/cm2) for 1.5 h contained approximately 0.15 ml fluid with a protein content of 40-50% of that in plasma, the main protein fractions being present in the same ratio as in plasma. 2 g sulfaisodimidine was given as bolus injection, i.v. infusion or orally to groups of 4 volunteers. The peak blister fluid concentrations after oral administration (120 +/- 18 mmol/l) was only marginally lower than the concentrations after i.v. infusion (122 +/- 28 mmol/l) and i.v. bolus injections (134 +/- 37 mmol/l). The total drug blister fluid concentration started to decrease before the plasma level was reached. However the relative concentration increased from 53% of that in plasma at 8 h to 66% at 12 h after drug administration. Considering the protein binding of the drugs, the interstitial fluid levels of free drug were presumably higher than the plasma level after 8 h. Comparison of drug concentrations in blisters produced before and after the drugs were given showed higher concentrations in the latter for the first 2-6 h. However, after 8-12 h the concentrations of the drugs in the two types of blisters were similar. The suction blister method produces blisters of uniform size. The drug concentrations in different experiments showed the coefficient of variation for blister fluid concentrations to be no greater than for plasma levels. The consistent results of the standardized suction blister method makes this method useful for studying drug penetration to extravascular compartments in humans.
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Disorders and drug use were analysed in 885 infants whose mothers responded to a questionnaire approximately four months after birth in Oslo, Norway in 1985. Breast-feeding had no influence on drug use in infants, though a lower incidence of some disorders (diarrhea, constipation, vomiting) was found in infants who were breast-fed for average four months than in infants who were weaned earlier. Use of drugs in infants was positively associated with use of drugs by the mother and with the length of her education. About 75% of the babies had at least one disorder and 60% had received at least one drug during the four month registration period. It was claimed that 85% of the drugs were recommended by a physician or a nurse. Anticolic agents, respiratory agents and dermatologicals were given frequently. The single most used drug was dimethicone. 98% of the 261 infants with colic syndrome were treated with this surface active drug, which has an efficacy similar to placebo. During a two week period preceding registration 12% of all infants and concomitantly 25% of the breast-fed infants were exposed to drugs at least once. The drug intake through breast milk was calculated to be 1/7 of the total drug use (117 infant Defined Daily Doses/1,000 infants/day) in breast-fed babies. Validation of the answers to the written questionnaire by subsequent interview of 96 mothers revealed considerable underreporting in the former; 33% for disorders, 22% for drugs and 18% for infant doses. It is concluded that medication for minor disorders in infancy is quite extensive and often unnecessary. Further informative efforts should be directed at parents, as well as the health workers involved.