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BACKGROUND AND OBJECTIVE: Use of statins is considerable among older persons. We investigated factors associated with statin discontinuation in new statin users aged 70 years or older within the first 4 years of use. DESIGN: Register‐based descriptive drug utilization study using data from 2008 to 2016. POPULATION/SETTING: All Danish persons, aged 70 years or older, initiating statin treatment. MEASUREMENTS: Rates and predictors of statin discontinuation after 1 year (early), 2 years, and 4 years. Predictors of discontinuation were estimated using logistic regression. RESULTS: We included 83 788 statin initiators. At 1 year, 13% had discontinued their treatment, while another 12% and 13% discontinued after 2 and 4 years, respectively. The overall discontinuation rate over 4 years was 32%. Increasing age was associated with discontinuation at all time points (adjusted odds ratio [OR] = 2.06 [95% confidence interval {CI} = 1.35‐3.16] at 1 year, adjusted OR = 3.94 [95% CI, 1.83‐8.49] at 4 years, comparing those aged >95 years to those aged 70‐74 years). Further, higher comorbidity scores and use of more than 10 medications were modestly associated with discontinuation. Use of statins for secondary prevention was associated with decreased odds of discontinuation compared to primary prevention at 1 year (adjusted OR = 0.74; 95% CI, 0.65‐0.83) and at 4 years (adjusted OR = 0.83; 95% CI, 0.72‐0.95), along with concomitant use of cardiovascular (CV) therapies. The annual proportion of early discontinuers ranged from 14% to 17% for primary prevention and from 9% to 12% for secondary prevention between 2008 and 2015. DISCUSSION: Statin discontinuation within the first 4 years after initiation appeared to be influenced most strongly by age, and may also be influenced by comorbidity, polypharmacy, use for secondary prevention, and concomitant CV medication use. Future research should clarify reasons for, and discussions about, statin discontinuation and initiation among older persons, to provide additional insight on this topic. J Am Geriatr Soc 67:2050–2057, 2019 [ABSTRACT FROM AUTHOR]

Dr. Olli Kärkkäinen from the University of Eastern Finland has been awarded the BCPT Young Researcher Nordic Prize in Basic & Clinical Pharmacology & Toxicology for 2023. He has made significant contributions to the field of Pharmacology and Toxicology. Dr. Kärkkäinen has a PhD in pharmacology and has been actively involved in teaching and research activities. His main research interest is studying the effects of different exposures on metabolic processes in the body. He has authored numerous scientific articles, book chapters, and is involved in various scientific committees and organizations. Dr. Kärkkäinen is also a co-founder of Afekta Technologies Ltd and has received research grants and holds a patent. [Extracted from the article]

Professor Eeva Moilanen has been awarded the BCPT Nordic prize for her significant contributions to the field of pharmacology and toxicology. She has conducted extensive research on inflammation, treatment targets, and molecules for osteoarthritis and allergic disease. Moilanen has published over 400 papers, supervised 30 PhD students, and served in various leadership roles in pharmacological societies. Her work has had a profound impact on the field of pharmacology over the past 30 years. [Extracted from the article]

GRAPH Professor, DMSc, Kim Brøsen has been awarded the BCPT Nordic Prize for 2022 in Basic and Clinical Pharmacology and Toxicology. The BCPT Nordic Prize 2022 goes to Professor Kim Brøsen Kim Brøsen has served on editorial boards for major journals within the field of clinical pharmacology including Clinical Pharmacology and Therapeutics and British Journal of Clinical Pharmacology. [Extracted from the article]

GRAPH Tore Bjerregaard Stage has been awarded the BCPT Young Researcher Nordic Prize for 2022 in Basic and Clinical Pharmacology and Toxicology. Both are clinically very important drug-drug interactions that should be taken into account when planning pharmacotherapy. [Extracted from the article]

Objective. General practitioners’ (GPs’) perception of risk is a cornerstone of preventive care. The aims of this interview study were to explore GPs’ professional and personal attitudes and experiences regarding treatment with lipid-lowering drugs and their views on patient compliance. Methods. The material was drawn from semistructured qualitative interviews. We sampled GPs purposively from ten selected practices, ensuring diversity of demographic, professional, and personal characteristics. The GPs were encouraged to describe examples from their own practices and reflect on them and were informed that the focus was their personal attitudes and experiences. Systematic text condensation was applied for analysis in order to uncover the concepts and themes. Results. The analysis revealed the following 3 main themes: (1) use of cardiovascular guidelines and risk assessment tools, (2) strategies for managing patient compliance, and (3) GPs’ own risk management. There were substantial differences in the attitudes concerning all three themes. Conclusions. The substantial differences in the GPs’ personal and professional risk perceptions may be a key to understanding why GPs do not always follow cardiovascular guidelines. The impact on daily clinical practice, personal consultation style, and patient behaviour with regard to prevention is worth studying further. [ABSTRACT FROM AUTHOR]

Background. Internet-based complex interventions aiming to promote weight loss and optimize healthy behaviors have attracted much attention. However, evidence for effect is lacking. Obesity is a growing problem, resulting in an increasing demand for cost efficient weight loss programs suitable for use on a large scale, for example, as part of standard primary care. In a previous pilot project by Brandt et al. (2011) without a control group, we examined the effects of online dietician counseling and found an average weight loss of 7.0 kg (95% CI: 4.6 to 9.3 kg) after 20 months. Aims and Methods. To analyze the effects of a complex intervention using trained dieticians in a general practice setting combined with internet-based interactive and personalized weight management support compared with conventional advice with a noninteractive internet support as placebo treatment in 340 overweight patients during a 2-year period. Primary endpoints are weight loss and lowering of cholesterol (LDL). We will also explore patients' sociodemographics and use of the intervention as well as the health professionals' views and perceptions of the intervention (their role and the advice and support that they provide). Perspective. The project will generate knowledge on the cost-effectiveness of a complex internet-based intervention in a general practice setting and on barriers and acceptability among professionals and patients. [ABSTRACT FROM AUTHOR]

A sample of 3,201 Danes was subjected to personal interviews in which they were asked to state their preferences for risk-reducing health care interventions based on information on absolute risk reduction (ARR) and relative risk reduction (RRR). The aim of the study was to measure the relative weighting of different types of risk information under various circumstances. The effect of presenting questions, and of explicitly formulating RRR, was analyzed. A preference for increases in RRR was demonstrated. There was a stronger inclination to choose the intervention that offered the highest RRR if RRR was explicitly stated. Individuals with more than 10 years of schooling also demonstrated a preference for increased ARR, but only when facing individually framed choices. In a social choice context, preferences for RRR remained intact, but the magnitude of ARR had no impact on choices. Results imply that social framing may induce a propensity to prefer interventions that target high-risk populations. Those respondents who had received ≤10 years of schooling demonstrated preferences for RRR but not ARR, and no impact of social framing was observed. [ABSTRACT FROM AUTHOR]

The risks associated with environmental exposures to inorganic mercury are typically assessed based on toxicity studies conducted with the soluble salt, mercuric chloride (HgCl2). Evidence indicates, however, that inorganic mercury is present in soil as a variety of compounds and that oral absorption of inorganic mercury decreases with a decrease in the solubility of the mercury compound being studied. Thus, while HgC l2) is approximately 15-20% bioavailable, the bioavailability of cinnabar (HgS) may be 30- to 60-fold less.The solubility and, hence, bioavailability of inorganic mercury in soil is expected to be substantially less than that of HgC l2) due to the presence of less soluble compounds and their interactions with soil constituents. Quantification of this difference in bioavailability is important in assessing potential risks associated withexposure to mercury-containing soil. A review of available studies supports the expectation that mercury bioavailability in soils will bereduced. This paper reviews methods for assessing soil metal absorption with consideration of the characteristics of the oral absorption of elemental and inorganic mercury that should be evaluated in designing additional studies. Because of the very slow elimination of mercury in some species, it is recommended that a repeated-dose study be conducted. Such a study would yield an estimate of relative bioavailability based on a comparison of tissue mercury concentrations in animals ingesting soil with those of animals receiving HgC l2).The dose, age, gender, and species of animal selected are not expected to affect relative bioavailability estimates; however, it is recommended that studies be conducted in two animal species. Rats should be used because they have been used in many studies of mercury absorption and toxicity. A species of large animals such as monkeys, swine, or dogs should also be used to provide confirmation in a species withgrea [ABSTRACT FROM AUTHOR]

This article reports the time course for deposition of methyl mercury administered as a single oral dose in whole body, total carcass, liver, kidneys, brain, blood, fat, muscle, bone, skin and hair of male and female Bom:NMRI mice. The whole-body elimination initially approximated first order kinetics with half-times around 7 days and 12 days for males and females respectively, although a decreased elimination rate was observed during the last 10 days. The elimination of mercury from carcass was slower than the elimination from the whole-body, causing an increasing relative carcass deposition with time in both male and female mice and explaining the observed deviation from first order elimination kinetics. Thus, first order kinetics is observed only during 2-3 weeks after dosage. Throughout the experimental period, male mice had significantly lower levels of mercury in both blood, brain and muscles than had female mice, whereas renal deposition of mercury in male mice was significantly higher than in female mice. At day 30 the females had about twice as much mercury in liver, brain and hair (median values) as had male mice. Despite the fact that comparable whole-body retention and carcass deposition were observed in male and female mice, the blood concentrations in male mice was only about half that in female mice. Furthermore, half-times for mercury in blood did not differ much between male and female mice and were close to whole-body half-time in male mice, although the absolute amounts of mercury in both blood and whole-body at day 20 were significantly different. The large sexual differences in mercury levels in tissues compared with the more limited differences in half-times and the fact that several organs have different mercury levels already at day 3 after dosage, although the whole-body levels are more or less equal, indicate extensive differences in the methyl mercury toxicokinetics between male and female Bom:NMRI mice. [ABSTRACT FROM AUTHOR]

The toxicokinetics of methyl mercury is studied most intensively in the rat. However, the toxicokinetics of methyl mercury in man is closer to the toxicokinetics in the mouse. This study describes the effects of dose, route of administration, and strain and sex on the toxicokinetics of methyl mercuric chloride in mice. Half-time values, fractional whole-body retentions and relative organ distributions of mercury were compared after a single oral or intraperitoneal administration of methyl mercuric chloride. The intestinal absorption was almost complete in accordance with earlier published results. The route of methyl mercury administration did not affect the whole-body retention of mercury significantly, but male mice retained lower amounts of mercury than did female mice. The elimination of mercury was demonstrated to follow first order kinetics during the two week study period independently of administration route, strain or sex. An inverse relationship between administered dose and whole-body retention was observed and by indirect evidence demonstrated not to be caused by an effect on the intestinal uptake mechanism. Absorbed and retained mercury at day 14 was primarily deposited in the carcass, but major deposits were also found in liver, kidneys and intestinal tract. Dose and route of administration did not affect the relative organ distribution of mercury significantly. However, the relative kidney deposition in male mice was about twice that in females. A significant difference in whole-body retention of mercury was observed between different strains of inbred mice at day 14 after administration. The relative organ distribution of mercury also varied significantly between different strains of mice. [ABSTRACT FROM AUTHOR]

Suppression of absorption by macromolecular chelators have been successful with several metals. In this paper a series of immobilized chelators ranging from DTPA to S-containing soft bases have been syntetized and investigated for ability to suppress intestinal uptake of 109Cd2+ in mice. Dextran-0-ethyl-mercaptan, xanthates derived from polysaccharides and polyvinyl alcohol, dithiocarbamates of polyethylene imine and aminoethyl cellulose, and DTPA immobilized on aminopropyl silica were all ineffective. DTPA immobilized on aminoethyl cellulose even enhanced the intestinal uptake. The macromolecular chelators were without extensive effect on organ distribution of absorbed cadmium, except for dithiocarbamate immobilized on polyethylene imine, which enhanced the deposition of cadmium in several organs including the brain. Although the results are discouraging, they indicate that design and synthesis of immobilized vicinal dithio compounds may represent an avenue for development of non-absorbable chelators with high affinity for cadmium. [ABSTRACT FROM AUTHOR]

The antidotal efficacies of chelators during acute cadmium intoxication has previously been examined in experiments where both a soluble cadmium salt and the chelator were administered parenterally. In the present study, PA, DMSA and related compounds were studied as oral antidotes during oral CdCl2 intoxication. According to the antagonistic effects noted on mortality, peristaltic toxicity and intestinal cadmium uptake, the relative efficacies of the compounds tested were: DMSA > PAD > DMPS > MSA > PA > NAPA. None of the chelators induced major changes in the organ distribution of absorbed cadmium, in particular no increased cerebral deposition of cadmium. This study indicates that, in oral cadmium intoxication in humans, orally administered DMSA would be likely to offer protection against the local toxicity of cadmium in the gastrointestinal tract as well as to reduce the risk of systemic toxicity of absorbed cadmium. [ABSTRACT FROM AUTHOR]

The article focuses on a study that aims to examine the interaction of SiO2 Nanoparticle (NP) with the skin and also investigate the penetration and permeation of these NP through human skin. The stratum corneum (SC) is considered to be the main rate-limiting factor for drug permeation across skin and is the primary skin barrier. The human skin samples were taken from female donors who had undergone breast surgery. The in vitro experiment showed that SiO2 NPs do not permeate through the skin.