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The conventional stereologic procedure for estimating bone surface densities in iliac crest biopsies gives biased estimates because bone substructure is anisotropic and the sectioning of the biopsies is intended to be parallel to the cylindrical axis of the iliac crest biopsy. It has recently been shown that random anisotropic sections with an identifiable axis or direction that is arbitrary but fixed can be used for unbiased estimates of surface areas. The arbitrary axis is called "vertical," which does not imply anything about its relation to direction of gravity. To describe the methodology and the practical sampling procedure for vertical sections, surface density of trabecular bone was estimated in 16 bone samples obtained at autopsy from eight persons (mean age 64 years) using an anisotropic cycloid test system designed for vertical sections. In addition, variation in the estimation procedure was quantitated. The average surface density of trabecular bone was 2.8 +/- 0.4 mm-1 (+/- SD). No systematic difference was observed between the two bone specimens from each of the eight persons. Estimation of the variance at each level of sampling showed that the majority of the total observed variance was due to true variance between individuals. Vertical section is, in general, the method of choice when dealing with surfaces not known to have an isotropic orientation distribution. The cycloid test system is easy and fast to use, and the estimate is truely unbiased. The requirements are all sections must be parallel to the vertical axis, the rotation around this axis must be random, the position of the section or of the biopsy must be random, and the vertical axis must be identified in the section.

The aim of this study was to test whether dental fluorosis can be produced by administration of chronic doses of fluoride during only the post-secretory stage of enamel mineralization. Eight control and eight experimental pigs matched by weight and litter were fed a low-fluoride diet (-/kg b.w. daily) from weaning to slaughter at 14 months. The test group received an oral dose of 2 mg F -/kg b.w. per day from 8 months of age. Lower fourth pre-molars were at the post-secretory stage at the start of fluoride administration (confirmed by tetracycline marker) and were just erupting at slaughter. All of the fourth pre-molar teeth from the test group developed diffuse enamel hypomineralization indistinguishable from human fluorosis. No such lesions were seen in any of the teeth from the control animals. It was concluded that enamel fluorosis may be caused by fluoride exposure in the maturation phase only. The pathogenic mechanism may be an effect either on the selective loss of protein or on the influx of mineral, both of which occur during the post-secretory or maturation stage of enamel formation.

The aim of the investigation was to measure the effect of fluoride on vertebral trabecular bone compressive strength and to correlate this with fluoride-induced changes in bone density. This correlation would express changes in the quality of bone during fluoride treatment. Pigs were used in the experiment because their trabecular bone structure and remodeling sequences are very similar to the human. Eight animals receiving a supplement of 2 mg F-/kg b.w. per day from age 8-14 months were compared with 8 control animals. Morphologic measurements in the animals receiving fluoride supplement showed a significant increase of 17% in bone density and a smaller, insignificant increase of 3% in ash weight analyses. Meanwhile, the mechanical parameters for the fluorotic animals were unchanged (maximum compressive strength, maximum stiffness, and energy-absorption capacity) or decreased (normalized compressive strength = maximum compressive load corrected for ash density). It is concluded that the increased bone mass during the initial stages of fluoride treatment does not necessarily indicate an improved bone quality. The discrepancy between bone mass and strength could be either a permanent or a temporary phenomenon and requires further investigation.

The three-dimensional (3-D) thickness of lamellae in normal trabecular bone was estimated by means of a stereologic transformation of the apparent width measured on 7 mm stained sections of undecalcified iliac bone from 65 nondiseased individuals aged 16--90 years. The average 3-D thickness of double lamellae (one bright and one dark) was 6.4 mm with a coefficient of variation between individuals of approximately 5%. Among the 32 males, the thickness was unchanged with age, while double lamellar thickness increased with age in the females [thickness (mm) = 5.980 (mm) ;.008 (mm/year) x age (yr). Intra-individual distributions of the thickness of double lamellae resembled normal distributions and had a median coefficient of variation of 23%. Within the trabecular osteons, no correlation between lamellar number and thickness was demonstrated, and no difference in thickness was found between mineralized and nonmineralized lamellae. Redeterminations showed no intra-observer bias in the estimation of the mean double lamellar thickness. The low variance between individuals indicated that the lamellar thickness is important for some essential biologic function, most likely the mechanical strength of trabecular bone. It may, therefore, be a useful variable to study in metabolic bone diseases. Furthermore, counting lamellae may be a simple way of estimating the 3-D thickness of remodeling sites in trabecular bone.

The mean wall thickness of iliac trabecular bone packets was determined in undecalcified iliac crest bone specimens from 14 hypothyroid patients, 14 hyperthyroid patients and 28 age- and sex-matched normal controls. Calcification rate and fractional resorption, formation and labeled surfaces in trabecular bone from the patients were measured by conventional histomorphometric methods after double-labeling with tetracycline. The mean wall thickness was increased in the hypothyroid patients (58,9 microns), while no change was demonstrated in the hyperthyroid group (52,5 microns) as compared to the controls (54,0 microns). Calculated estimates of trabecular bone remodeling at the "Basic Multicellular Unit" level showed longer periods of resorption, formation and total remodeling in the hypothyroid than in the hyperthyroid patients.

Blood samples from a group of 130 dentists and a control group of 40 blood-donors were analyzed by cold vapor atomic absorption spectrophotometry in order to evaluate the extent of mercury exposure. The median blood concentration of mercury was 4.0 (range: 1.2-19.2) micrograms/l for dentists and 2.0 (1.1-4.6) micrograms/l for controls (2P less than 0.01). Practice characteristics obtained in a questionnaire showed no statistically significant relationship to blood mercury, but 49 dentists having one or more fish meals per wk, had a median concentration of mercury, which was 47% higher than dentists seldomly consuming fish (2P less than 0.01). It was concluded that none of the examined dentists had blood concentrations above the level (35 micrograms Hg/l) associated with the hygienic threshold limit.

The wall thickness of completed remodeling sites in trabecular bone was estimated in 25 normal individuals and 5 patients with arthrosis of the knee, using 7 μm sections of undecalcified iliac crest bone. A systematic sampling procedure which gives a surface referent estimate of the thickness was applied. The efficiency of the sampling design was optimized by means of a cost-variance analysis. The proposed method of sampling which eliminates a common bias in bone histomorphometry is recommended for determinations of wall thickness, osteoid thickness, lamellar thickness, and distance between fluorochrome markers in trabecular bone. The intraindividual distributions of three-dimensional wall thickness were reconstructed from the measurements of apparent width by an unfolding procedure based on the geometric probability density function pertaining to randomly sectioned plates. Distributions of true wall thickness for the young normal individuals were unimodal and resembled normal distributions. The three-dimensional mean wall thickness was 61.4 ± 4.4 μm (± SID). It was demonstrated that the conventionally applied stereological transformation, which calculates the three-dimensional mean wall thickness from the mean apparent width by multiplying the latter by π/4, underestimates the three-dimensional mean wall thickness. An improved transformation is illustrated and is recommended for estimating three-dimensional mean thickness of plates from two-dimensional measurements in trabecular bone.

2 Dear Editor, The incidence of genital warts (GW) in young Danish women has recently been reported to have decreased “strongly” (1) after the implementation of the quadravalent vaccine against Human Papillomavirus (HPV). Monitoring the effect of HPV vaccination is important. The vaccine was licensed based on the outcome of randomized controlled trials (2-3). The trial populations were, however, somewhat selected including for instance only women with 4 or less life-time sexual partners. Blomberg and colleagues compared GW incidence in vaccinated (at least one time) and unvaccinated women. Vaccination was identified from the National Health Insurance Service Register, for women vaccinated within the free vaccination program, and from the National Prescription Register, for women who bought the vaccine themselves. The authors included five birth cohorts, where the proportion of vaccinated women varied from 14% in the oldest cohort born 1989-1990 to 87% in the youngest cohort born in 1997-1999. GW incidence was measured based on treatments in out-and inpatient hospital wards as recorded in the National Patient Register. The hazard ratio (HR) of GW incidence in vaccinated versus unvaccinated women was 0.62 for those born 1989-1990 decreasing to 0.12 for those born 1995-1996. No case occurred for vaccinated women born 1997-1999. In interpretation of these findings the reader should be aware of some reservations. Firstly, the registration of vaccinations is not comprehensive as vaccines bought by physicians and not used within the free vaccination program are not registered. This is, however, not

Until recently, Denmark has had the highest use of strong opioids per capita in the world. Our aim was to analyze cancer patients' use of opioids in this population by linkage between the Danish Cancer Register and a prescription database. The changes in opioid use from 1994 to 1998 in the entire cohort of cancer patients (n=24,190) in a Danish county (n approximately 470,000) were analyzed. The overall consumption of opioids increased from 20 kg to 37 kg oral morphine equivalents (omeq) per year. The average consumption increased from 7.6 to 10.7 g omeq/opioid user/year. The annual proportion of users increased from 17% to 20%. The proportion of patients who were alive 2 years after their first opioid prescription increased from 38% to 55%. Increased awareness towards pain treatment, with earlier initiation of opioid treatment and higher doses to the cancer patients, could be major explanations for the increase in the cancer patients' use of opioids.

Objective: To analyse the occurrence of multiple drug use (polypharmacy, PP) in the population and to identify individuals particularly prone to PP. Methods: Data were derived from the Odense Pharmacoepidemiological Database (OPED) and covered all subsidised prescriptions during 1994 presented by inhabitants in the county of Funen (n= 466 567). The number of individuals concurrently using two to four drugs (minor PP) and five or more drugs (major PP) was calculated on a random day in 1994. Drugs were classified according to the Anatomical Therapeutical Chemical (ATC) classification index. The main therapeutic class (second level of the ATC code) was used as an indicator for the type of health problem. A stepwise backwards logistic regression was used to identify predictors of major PP. Odds ratios were calculated for different drug classes, and the age and sex of all drug users. Results: On a random day, 8.3% of the population were exposed to minor PP and 1.2% to major PP. The prevalence of PP increased with age, and from the age of 70 years, two thirds of all drug users were PP users. Drug use was 50% more prevalent among women than men, but over the age of 70, the sexes did not differ in the prevalence of major PP. Many different drug combinations were found, and among major PP users (n= 5443), two thirds had their own unique drug regimen, different from all other drug users. Cardiovascular drugs and analgesics were often involved in PP among the elderly, while asthma drugs, psychotropic drugs and anti-ulcer drugs were predominant among young individuals exposed to PP. The odds ratio (OR) for major PP was substantially increased for individuals treated for cardiovascular diseases (OR, 4.5), anaemia (OR, 4.1) and respiratory diseases (OR, 3.6). Conclusions: PP is widespread in the population. Clinicians and organisers who are responsible for quality assurance programmes should intensify their surveillance of the groups most prone to PP (the elderly and those using analgesics or drugs for cardiovascular disease, anaemia, asthma and diabetes).

To better understand the reasons for lack of impact of sending feedback on prescribing pattern to general practitioners (GPs).Semi-structured interviews with GPs who had all participated in intervention studies addressing effects of prescriber feedback. Interviews were audiotaped and fully transcribed. Transcripts were studied repeatedly and coded into categories in order to produce meaningful patterns.None of the GPs believed they altered prescribing practice after they received prescriber feedback. Unsolicited prescriber feedback was perceived as violating the GPs' autonomy. The GPs wanted to decide for themselves what data should be sent to them. Aggregated data were difficult to interpret, and GPs did not regard it as a problem that their practice pattern deviated from that of other practices. There was a mistrust of the validity of data, and the GPs wanted to be able to identify the patients with a need for optimised therapy directly from the information provided in the prescriber feedback. In addition they wanted advice on how to optimise therapy.Postal prescriber feedback (not revealing the patients' identities) is not effective because it does not motivate GPs to change nor does it address the barriers to change. Prescriber feedback requested by the GPs may be more effective, however, if it includes identities of inappropriately treated patients combined with relevant advice on how to optimise prescribing.

1359-6349/$ see front matter Copyright 2013 ECCO the European CanCer Organisation. All rights reserved. http://dx.doi.org/10.1016/j.ejcsup.2013.07.053 * Corresponding author at: Department of Gynecology and Obstetrics, Odense University Hospital and Institute of Clinical Res Boulevard 29, 5000 Odense C, Denmark. Tel.: +45 6541846. E-mail address: Marianne.thygesen@rsyd.dk (M.K. Thygesen). M.K. Thygesen *, B.D. Pedersen , J. Kragstrup , L. Wagner , O. Mogensen a,d

To assess whether the frequency of antibiotic prescriptions to patients with respiratory infections is reduced when general practitioners (GPs) use a C-reactive protein (CRP) rapid test in support of their clinical assessment, and to study whether using the test will have any effect on the course of diseaseRandomised controlled trial.35 general practices, County of Funen, Denmark.812 patients with respiratory infection.Frequency of antibiotic prescriptions and morbidity 1 week after the consultation, as stated by the patients.In the CRP group the frequency of antibiotic prescriptions was 43% (179/414) compared with 46% (184/398) in the control group (odds ratio (OR) = 0.9, NS). After 1 week, increased or unchanged morbidity was stated more frequently in the CRP group (12%) than in the control group (8%) (OR = 1.6, p = 0.05). In the control group, the variable having the greatest influence on whether the GP prescribed antibiotics was the patients' general well-being (OR = 2.9, p0.0001), whereas in the CRP group the CRP value had the greatest influence (OR = 1.1 per unit increase (mg/l), p0.0001).Based on the present study, the use of the CRP rapid test in support of a possible antibiotic treatment for respiratory infections in general practice cannot be recommended.

The use of antidepressants (ADs) has escalated and prompted considerable debate. Many depressed patients go unrecognised or under-treated and the area of indication of the new ADs is widening. The aim of this study was to analyse (i). the variation in general practitioners' prescribing of ADs by comparing with prescribing of other drug groups and (ii). whether the general prescribing behaviour, practice activity and demography are associated with the AD prescribing.Analysis of AD prescribing patterns among 174 general practices (93.5%) in the County of Funen, Denmark. Age- and sex-standardised 1-year incidences and prevalences of AD prescribing for patients listed were calculated using individual prescription data from Odense University Pharmacoepidemiologic Database. Data about health services and practice demography were obtained from the Health Insurance Register. The variation in AD 1-year prevalence was compared with other drug groups by a variation index (90%/10% percentile). Univariate linear regression analysis was used to examine associations between practice characteristics and prescribing.The 1-year prevalence of AD prescribing varied sixfold, no more than the prevalence of five other drug groups. Practices with high yearly: general prescribing prevalence, mean number of drugs per medicated patient, number of surgery consultations/100 patients and counsellings/100 surgery consultations showed the highest yearly prevalence of AD prescribing. Single-handed practices had higher AD prescribing rates than partnerships. The relative use of selective serotonin re-uptake inhibitors and other new ADs showed only little variation (10% and 90% percentiles as close as 66-86%), but practices with high 1-year prevalence and incidence most often chose the new ADs.Analysis of inter-practice variation showed no extraordinary quality problems with regard to AD prescribing, but does not exclude that there might be problems. The general prescribing pattern of the general practitioners seems essential to their attitude to AD prescribing. The relationship between counselling and prescribing was a feature specific to ADs and deserves further investigation. Quality indicators are needed to understand differences in AD prescribing, and studies based on prescription data have to be supplemented with individual clinical data.

To analyse agreement between patients' and GPs' perceptions of risk factors and overall risk of ischaemic heart disease (IHD).Cross-sectional study based on paired information from patients and GPs.Twenty-six GPs in the County of Ringkøbing, Denmark, participating in a medical audit during 3 weeks in May 1999.252 patients with IHD and 1239 without IHD.GPs and patients were asked about specific risk factors for IHD and their perception of overall risk. Their agreement was evaluated by Kappa statistics.Agreement between GPs and patients varied from 70% to 97%. Disagreement was observed most often for patients with IHD and patients listed with elderly GPs (50 years). Generally, patients perceived the overall risk of IHD lower than their doctors, and for most patients with a perception of low risk the GP estimated the risk as high.Patients and GPs have different perceptions of the risk of [HD. This may be due to different perceptions of the importance of specific risk factors and different reference frames for risk perception. GPs have an important role in communicating the meaning of risk factors and interventions should be considered to improve risk communication in general practice.

20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:162

INTRODUCTION: Pandemics are known to cause stress and anxiety in pregnant women. During the coronavirus disease 2019 (COVID-19) lockdown of the Danish society, pregnant women were considered to be at increased risk, and access to antenatal care changed. METHODS: On 8 April 2020A, a questionnaire was sent to 332 pregnant women previously sampled by general practitioners in two Danish regions. The women were contacted via secured e-mail (e-Boks), and questionnaires were returned until 6 May. RESULTS: The questionnaire was returned by 257 women (77%). More than half believed that they were at a high risk of infection with COVID-19, and a third of the women were concerned about the risk of serious disease – especially for their unborn child. Almost 90% isolated at home most of the time. The majority were worried about possible consequences of the pandemic for antenatal care, but very few had actually missed a scheduled preventive consultation with their general practitioner, and only 15% had missed an appointment with their midwife. The majority of the women preferred normal consultations and found no added safety in shifting the consultation from the normal clinical setting. CONCLUSIONS: The COVID-19 pandemic and lockdown have had a major impact on Danish pregnant women. Even so, concerns were more focused on access to care than on the risk of COVID-19 infection. Contacts with the antenatal healthcare system have only been moderately affected.

INTRODUCTION: Uncertainty and risk are central issues in relation to health and health care services. Healthy individuals do not necessarily fall ill, despite the presence of risk factors. Doctors, health service administrators, and patients are more inclined to choose interventions against risk factors, when information about the effects is presented in terms of relative risk reductions rather than absolute risk reductions. The aim of the study was to gain better insight into how general practitioners (GPs) perceive risk of disease, and whether this perception depends on the risk reduction being presented in absolute or relative terms. MATERIAL AND METHODS: Questionnaires with clinical episodes were sent to 1500 Danish GPs. The GPs were randomised into four groups of 375, all of whom received the same case history with information about risk reduction achieved through medical treatment phrased in terms of either relative risk reduction, absolute risk reduction, number needed to treat, or all of the aforementioned terms of risk reduction. The GPs were asked whether they would recommend medical treatment as primary prevention, knowing the case history and expected risk reduction. RESULTS: The GPs' attitude towards recommending medical treatment depended on the phrasing of risk reductions. Of the doctors who received all information on risk reductions, 72% would definitely or probably recommend medication, whereas 91% would recommend medication if only information about relative risk reduction was given, and 63% would recommend medication if information was given in terms of absolute risk reduction or number needed to treat. DISCUSSION: To advise patients rationally, knowledge of the patients' preferences, as well as consideration of all available measures of risk reductions, is needed. Udgivelsesdato: 2002-Nov-11

Cross-sectional osteon size was measured in undecalcified stained sections of iliac crest bone specimens from normal individuals (n = 68) and from patients with spinal osteoporosis (n = 27), primary hyperparathyroidism (n = 23), epilepsia (receiving chronic anti-convulsant therapy) (n = 11), acromegaly (n = 18), and hypothyroidism (n = 12). In each individual the shortest osteon diameter (D) and the corresponding Haversian canal diameter (d) were measured in a minimum of 20 completed secondary osteons by means of a micrometer eyepiece. Among normal males the areas of bone resorbed and formed increased with age (p less than 0.01), owing to an increase in the thickness of bone resorbed (p less than 0.01) and an unchanged thickness of bone formed. Among the females, both the areas of bone resorbed and formed decreased with age (p less than 0.05), owing to a reduction in the thickness of bone resorbed (p less than 0.05) as well as formed (p less than 0.001). Resorbed and formed areas were reduced in the epileptic (p less than 0.01) and acromegalic (p less than 0.01) groups but increased in the hypothyroid group (p less than 0.01) compared to sex- and age-matched controls. Neither the osteoporotic nor the hyperparathyroid group showed any alterations in osteon size. The Haversian canal diameter was slightly increased in the epileptic group but normal in the other patient groups. The observed changes reflect variations in the amount of work performed by osteoclasts and osteoblasts during bone remodelling and may be explained by variations in cellular activity and bone turn-over rates.

Most antidepressant treatment is initiated and continued in general practice but, despite current guidelines, treatment duration is often short among patients with depression. Discontinuation may, however, be caused by a complexity of factors, but so far research has focused on drug effects, adverse effects and drug regimens.Our aim was to analyse whether early discontinuation of first-time antidepressant treatment in general practice may be predicted by (i) social position and psychiatric history of the patient; and (ii) demography, practice activity and the general prescribing behaviour of the GP.Early discontinuation, i.e. that patients do not purchase antidepressants in the 6 months following first prescription, was analysed using established databases. Among patients presenting in 174 general practices in Funen County, Denmark, 4860 adult first-time users of antidepressants were identified (regardless of diagnosis). The inclusion period was January 1998-June 1999.One in three patients did not purchase antidepressants in the 6 months following first prescription, but rates were higher among those prescribed tricyclic compared with new generation antidepressants. Patients' age and sex did not have an influence, but early discontinuation was more frequent among patients of low socio-economic status and patients prescribed in practices characterized by high prescribing rates. No association with psychiatric history was observed.Early discontinuation is frequent in general practice, and patients of low social status are at greater risk. Adherence-promoting strategies should pay attention to the high prescribing doctors. Further studies may answer the question of whether the association between doctors' prescribing behaviour and early discontinuation is a feature specific to antidepressants or a more general phenomenon.

pharmacology and Toxicology, Abstract book, 5th Congress of the European Association for Clinical Pharmacology and Therapeutics

Background Fragmentation in healthcare can present challenges for patients with suspected cancer. It can add to existing anxiety, fear, despair and confusion during disease trajectory. In some circumstances patients are offered help from an extra contact person, a Nurse Navigator (NN). Scientific studies showing who will benefit from the extra help offered are missing. This study aims to explore who could benefit from the help on offer from a nurse appointed as NN in the early part of a cancer trajectory, and what would be meaningful experiences in this context. Methods A longitudinal study with a basis in phenomenology and hermeneutics was performed among Danish women with gynecological cancer. Semi-structured interviews provided data for the analysis, and comprehensive understanding was arrived at by first adopting an open-minded approach to the transcripts and by working at three analytical levels. Results Prior experience of trust, guarded trust or distrust of physicians in advance of encountering the NN was of importance in determining whether or not to accept help from the NN. For those lacking trust in physicians and without a close relationship to a healthcare professional, the NN offered a new trusting relationship and they felt reassured by her help. Conclusions Not everyone could use the help offered by the NN. This knowledge is vital both to healthcare practitioners and to administrators, who want to do their best for cancer patients but who are obliged to consider financial consequences. Moreover patients’ guarded trust or distrust in physicians established prior to meeting the NN showed possible importance for choosing extra help from the NN. These findings suggest increased focus on patients’ trust in healthcare professionals. How to find the most reliable method to identify those who can use the help is still a question for further debate and research.

Wonca Europe regional region 2004. Book of abstracts.