Palle Mark Christensen

Subchronic toxicity of baltic herring oil and its fractions in the rat (III) bone tissue composition and dimension, and ratio of n-6/n-3 fatty acids in serum phospholipids

Pharmacological interventions for osteoporosis may reduce morbidity and mortality, but they incur additional health care costs. The aim was to quantify the additional costs and health benefits of prescribing alendronate 10 mg and calcium/vitamin D daily for 71-year-old women with a fracture risk twice that of the population average in stead of calcium/vitamin D alone. A state transition model based primarily on Scandinavian data was developed. Women were followed from age of 71 years until 100. Alendronate was assumed to reduce the fracture risk by 50%. Health benefits from the interventions were expressed in terms of life years, quality adjusted life years, and fractures avoided. Societal costs were estimated using literature estimates and Danish tariffs. All costs were measured in 2002 Danish Kroner (DKK). Future costs and benefits were discounted at 5% per year. The incremental cost per QALY gained was DKK125,000 while the cost per life year gained was DKK 374,000. The use of alendronate was cost-saving when 1) the treatment was extended to five years, 2) the risk of fracture was four times the population average, 3) the effect of alendronate was assumed to persist for three years after discontinuation of treatment, 4) a greater proportion had severe sequelae after a hip fracture, or 5) the start of therapy was delayed until age of 77 years. In conclusion, the use of alendronate compares well with other well established therapies in terms of cost-effectiveness in older women with high risk of fracture.

The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson's disease: A meta-analysis

The association between the sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinsons disease was examined in a meta-analysis of case-control studies. The odds ratio was calculated for the risk of Parkinsons disease among poor metabolisers compared with extensive metabolisers. Twenty-one studies were identified of which six were excluded because they were not reported as full papers (n = 3), used incomplete genotype analysis (n = 2) or used Parkinson patients as both control individuals and cases (n = 1). The overall odds ratio was 1.48 (95% confidence interval 1.10-1.99). The odds ratio was 1.05 (95% confidence interval 0.63-1.77) in studies discriminating extensive and poor metabolisers by phenotyping (n = 8) and 1.67 (95% confidence interval 1.11-2.50) in studies using genotyping (n = 7). This difference was caused by a single large study using genotyping. We conclude that there is no convincing evidence of an association between the debrisoquine/sparteine polymorphism and Parkinsons disease. However, it could prove worthwhile to perform another large study using genotyping.

The effect of statins on average survival in randomised trials, an analysis of end point postponement

Objective To estimate the average postponement of death in statin trials. Setting A systematic literature review of all statin trials that presented all-cause survival curves for treated and untreated. Intervention Statin treatment compared to placebo. Primary outcome measures The average postponement of death as represented by the area between the survival curves. Results 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively. Conclusions Statin treatment results in a surprisingly small average gain in overall survival within the trials’ running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered.

Associations between patients’ risk attitude and their adherence to statin treatment – a population based questionnaire and register study

BackgroundPoor adherence to medical treatment may have considerable consequences for the patients’ health and for healthcare costs to society. The need to understand the determinants for poor adherence has motivated several studies on socio-demographics and comorbidity. Few studies focus on the association between risk attitude and adherence. The aim of the present study was to estimate associations between patients’ adherence to statin treatment and different dimensions of risk attitude, and to identify subgroups of patients with poor adherence.MethodsPopulation-based questionnaire and register-based study on a sample of 6393 persons of the general. Danish population aged 20–79. Data on risk attitude were based on 4 items uncovering health-related as well as financial dimensions of risk attitude. They were collected through a web-based questionnaire and combined with register data on redeemed statin prescriptions, sociodemographics and comorbidity. Adherence was estimated by proportion of days covered using a cut-off point at 80 %.ResultsFor the dimension of health-related risk attitude, “Preference for GP visit when having symptoms”, risk-neutral and risk-seeking patients had poorer adherence than the risk-averse patients, OR 0.80 (95 %-CI 0.68–0.95) and OR 0.83 (95 %-CI 0.71–0.98), respectively. No significant association was found between adherence and financial risk attitude. Further, patients in the youngest age group and patients with no CVD were less adherent to statin treatment.ConclusionWe find some indication that risk attitude is associated with adherence to statin treatment, and that risk-neutral and risk-seeking patients may have poorer adherence than risk-averse patients. This is important for clinicians to consider when discussing optimal treatment decisions with their patients. The identified subgroups with the poorest adherence may deserve special attention from their GP regarding statin treatment.

Benign breast disease and breast cancer.

to the editor: The article on the risk of cancer in patients with benign breast disease by Hartmann et al. (July 21 issue) 1 contains some questionable assumptions. “Atypical ductal hyperplasia” and “lobular hyperplasia,” shown in Figure 1E and Figure 1F of the article, do not belong in the category of benign breast disease. Experienced pathologists know that the differentiation of the so-called atypical ductal hyperplasia from an intraductal carcinoma of the breast is extremely difficult in most cases and impossible in some. 2 Lobular hyperplasia, shown in Figure 1F, is closely related to lobular carcinoma in situ, recognized for generations as a precursor lesion of breast cancer. 3 Thus, these two types of lesions should be classified as precursors of mammary carcinoma, as demonstrated by a much higher rate of subsequent breast cancer in patients with these lesions than in patients with truly benign disorders. One would have expected an even higher rate of cancer in patients who were apparently not treated, except for excision of the lesion. The issue of lesion classification and risk is even more important if this information is shared with patients, as suggested by Elmore and Gigerenzer, in the accompanying editorial. 4

Benign breast disease and breast cancer [1] (multiple letters)

to the editor: The article on the risk of cancer in patients with benign breast disease by Hartmann et al. (July 21 issue) 1 contains some questionable assumptions. “Atypical ductal hyperplasia” and “lobular hyperplasia,” shown in Figure 1E and Figure 1F of the article, do not belong in the category of benign breast disease. Experienced pathologists know that the differentiation of the so-called atypical ductal hyperplasia from an intraductal carcinoma of the breast is extremely difficult in most cases and impossible in some. 2 Lobular hyperplasia, shown in Figure 1F, is closely related to lobular carcinoma in situ, recognized for generations as a precursor lesion of breast cancer. 3 Thus, these two types of lesions should be classified as precursors of mammary carcinoma, as demonstrated by a much higher rate of subsequent breast cancer in patients with these lesions than in patients with truly benign disorders. One would have expected an even higher rate of cancer in patients who were apparently not treated, except for excision of the lesion. The issue of lesion classification and risk is even more important if this information is shared with patients, as suggested by Elmore and Gigerenzer, in the accompanying editorial. 4

General practitioners’ experience of using a questionnaire when assessing cancer patients’ needs: a qualitative study

Background. International guidelines recommend health care professionals to use supportive tools like questionnaires when assessing cancer patients’ needs. Little is known about GPs’ perspectives and experience in this regard. Objective. To examine how GPs experience to involve a short questionnaire, completed by patients’ prior to a consultation, when addressing the patients’ problems and needs. The aim is to contribute to the knowledge concerning the use of questionnaires as part of clinical cancer care in general practice. Methods. Semi-structured individual interviews with 11 GPs in the Region of Southern Denmark purposefully sampled with regard to gender, years working in general practice and practice form. Interviews were analyzed using systematic text condensation. Results. Most GPs found that using the questionnaire provided a supportive structure to the consultation. The questionnaire helped to bring forward issues of importance to the patients, which might otherwise not have been mentioned and enhanced a patient-centered approach. A few GPs found the use of the questionnaire to be restraining, detracting focus from the patient and impede usual practice. Conclusions. This study shows that using questionnaires may have the potential to improve clinical cancer care in general practice in relation to needs assessment of cancer patients and the results support current recommendations.

Clinical Pharmacology in Denmark in 2016: 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality

The Danish Society of Clinical Pharmacology was founded in 1976, and mainly thanks to the persistent efforts of the society, clinical pharmacology became an independent medical speciality in Denmark in 1996. Since then, clinical pharmacology has gone from strength to strength. In the Danish healthcare system, clinical pharmacology has established itself as an indispensible part of the efforts to promote the rational, safe and economic use of drugs. Clinical pharmacologists are active in drug committees both in hospitals and in the primary sector. All clinical pharmacology centres offer a local medicines information service. Some centres have established an adverse drug effect manager function. Only one centre offers a therapeutic drug monitoring service. Clinical pharmacologists are responsible for the toxicological advice at the Danish Poison Information Centre at Bispebjerg University Hospital in the Capital Region. The Department of Clinical Pharmacology at Aarhus University Hospital works closely together with forensic toxicologists and pathologists, covering issues regarding illicit substances, forensic pharmacology, post-mortem toxicology, expert testimony and research. Therapeutic geriatric and psychiatric teach-inns for specialist and junior doctors are among the newest initiatives organized by clinical pharmacologists. Clinical pharmacologists work also in the Danish Medicines Agency and in the Danish pharmaceutical industry, and the latter has in particular a great growth potential for creating new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors) or approximately 12 specialists per one million inhabitants.