Multidisciplinary telephone conferences about medication therapy after discharge of older inpatients: a feasibility study.

Background Studies have shown poor post-discharge implementation by the general practitioner of changes made to patients' medication during admission. Objective To assess the feasibility of conducting telephone conferences delivering information about changes in older patients' medications from hospital to general practitioners. Setting Two departments of geriatric medicine in a Danish routine healthcare setting. Method Older polypharmacy patients (≥ 65 years and ≥ 5 prescriptions) consecutively admitted were eligible for inclusion. Telephone conferences based on a review of these patient's medication therapy during hospital stay were arranged between a pharmacist and a geriatrician from the hospital, and a general practitioner. Interviews were conducted with pharmacists, geriatricians, and general practitioners about their perspectives on the feasibility of telephone conferences. Interviews were analyzed using systematic text condensation. Main outcome measure The proportion of telephone conferences conducted and perspectives on the feasibility of the study. Results A total of 113 patients were included and 82 patients (75%) were eligible for telephone conferences. A total of 40 (49%) telephone conferences were conducted. The main reasons for conferences not being conducted were general practitioners not wanting to participate or not returning the calls from the pharmacists. Three themes emerged from the qualitative analysis: considerations on planning and running the project, Barriers, facilitators, and implications of the telephone conference, and Actual and desirable cross-sectorial communication. Conclusion Telephone conferences were only possible for half of the patients. The participating general practitioners, pharmacists and geriatricians expressed varied benefit and agreed that telephone conferences were mainly relevant for complex patients.

Postponement of Death by Statin Use: a Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: The average postponement of the outcome (gain in time to event) has been proposed as a measure to convey the effect of preventive medications. Among its advantages over number needed to treat and relative risk reduction is a better intuitive understanding among lay persons. OBJECTIVES: To develop a novel approach for modeling outcome postponement achieved within a trial's duration, based on published trial data and to present a formalized meta-analysis of modeled outcome postponement for all-cause mortality in statin trials. METHODS: The outcome postponement was modeled on the basis of the hazard ratio or relative risk, the mortality rate in the placebo group and the trial's duration. Outcome postponement was subjected to a meta-analysis. We also estimated the average outcome postponement as the area between Kaplan-Meier curves. Statin trials were identified through a systematic review. RESULTS: The median modeled outcome postponement was 10.0 days (interquartile range, 2.9-19.5 days). Meta-analysis of 16 trials provided a summary estimate of outcome postponement for all-cause mortality of 12.6 days, with a 95% postponement interval (PI) of 7.1-18.0. For primary, secondary, and mixed prevention trials, respectively, outcome postponements were 10.2 days (PI, 4.0-16.3), 17.4 days (PI, 6.0-28.8), and 8.5 days (PI, 1.9-15.0). CONCLUSIONS: The modeled outcome postponement is amenable to meta-analysis and may be a useful approach for presenting the benefits of preventive interventions. Statin treatment results in a small increase of average survival within the duration of a trial. SYSTEMATIC REVIEW REGISTRATION: The systematic review was registered in PROSPERO [CRD42016037507] .

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.

Associations between patients' risk attitude and their adherence to statin treatment - a population based questionnaire and register study.

BACKGROUND: Poor 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. METHODS: Population-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 %. RESULTS: For 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. CONCLUSION: We 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.

Completing a Questionnaire at Home Prior to Needs Assessment in General Practice: A Qualitative Study of Cancer Patients' Experience.

BACKGROUND: Systematic assessments of cancer patients' rehabilitation needs are recommended, and questionnaires are considered to be useful tools when making such assessments. OBJECTIVE: The aim of this study was to explore patients' experience of completing a questionnaire about their problems and distress at home prior to a needs assessment in general practice. METHODS: Sixteen patients were recruited by their general practitioners (GPs). Semi-structured interviews were conducted in the home of the participants and at the general practice, with one interview taking place over the phone. Data were analyzed using systematic text condensation. RESULTS: Twelve women and four men aged between 49 and 83 years of age, and diagnosed with various cancers between 1 month and 4 years ago, participated in the study. The results showed how the completion of a questionnaire at home provided patients with an opportunity to reflect on different problems, and the importance of these problems to the patient's everyday life, as well as an opportunity to articulate which problems they wanted to discuss with their GPs. CONCLUSIONS: The results demonstrate that completing a questionnaire seems to stimulate patients' ability to reflect on their situation, clarify the importance of different problems to their everyday lives, and articulate these considerations to their GPs. Furthermore, we have shown that a questionnaire has the ability to interact with the patient and instigate a process of awareness. It is important to acknowledge this process of interaction between patient and questionnaire as an important part of understanding how and why questionnaires may support the patient when completing a questionnaire prior to a clinical encounter.

GPs' Perceptions of Cardiovascular Risk and Views on Patient Compliance: A Qualitative Interview Study.

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.

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.

[Medical treatment of depression during pregnancy and breastfeeding]. / Medikamentel behandling af depression under graviditet eller amning.

Medical treatment of depression during pregnancy and breastfeeding often involves concern by both the patient and the doctor because of the fear of adverse reactions or malformations of the child. This article gives an updated review on how antidepressants, lithium, antipsychotics and ECT can be used during pregnancy and breastfeeding, and presents a treatment algorithm which is used at Odense University Hospital.

Number-needed-to-treat (NNT)--needs treatment with care.

The "number-needed-to-treat" (NNT) was introduced about 15 years ago and has gained widespread use. It has been claimed to be "easy to understand" and gives "intuitive meaning". When used to measure the effectiveness of interventions targeting chronic disease processes e.g. atherosclerosis and osteoporosis, NNT (as well as relative and absolute risk reduction) does not capture the crucial time component, a fact that has important consequences: NNT varies over time, it may not mean that adverse events (fractures, myocardial infarctions etc.) are avoided, but simply that they are postponed. Finally, empirical studies indicate that lay people and doctors misunderstand NNT. We recommend that NNT be used with considerable care. There is probably no single effect measure that is able to convey all necessary information.

Cost-effectiveness of alendronate in the prevention of osteoporotic fractures in Danish women.

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.

Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis.

The ideal treatment of osteoporosis should preferably prevent fractures through normalization of bone mass and bone micro-architecture. Biosynthetic human parathyroid hormone 1-34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2-3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 microg/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged.

A randomized trial of laypersons' perception of the benefit of osteoporosis therapy: number needed to treat versus postponement of hip fracture.

BACKGROUND: Information on the benefits of therapeutic interventions can be ex-pressed in various ways, including relative risk reduction, absolute risk reduction,and number needed to treat (NNT). An alternative to such risk-based measures is postponement of an adverse outcome (eg, hip fracture in the case of osteoporosis). OBJECTIVE: The goal of this study was to examine whether laypersons' perception of the benefit of an osteoporosis therapy differs when it is presented in terms of the NNT to avoid 1 hip fracture compared with the duration of postponement of hip fracture. METHODS: This was a cross-sectional, randomized, controlled trial. Face-to-face interviews of a representative sample of the Danish population were conducted in respondents' homes. Respondents were randomized to receive information about the benefits of a hypothetical osteoporosis intervention either in terms of different magnitudes of NNT (10, 50, 100, or 400) or different durations of postponement of hip fracture (1 month, 6 months, 1 year, or 4 years). Participants were subsequently asked if they would consent to the intervention. RESULTS: A total of 1728 individuals were contacted at home and asked if they would take part in a face-to-face interview; 967 (56%) were successfully interviewed. The age (mean age, 44.5 years; range, 20-74 years) and sex distribution (51% male, 50% female) of the sample was similar to that of the general Danish population. Based on NNTs of 10, 50, 100, and 400, the proportions of respondents who said they would consent to the intervention were a respective 65%,61%, 63%, and 57%. Increasing NNT was not significantly associated with a lower proportion of consent (test for trend chi-square(1)= 0.75; P = NS). Forty-three percent of respondents indicated that the concept of NNT was difficult to understand, and 38% interpreted NNT in a way that was probably incorrect. In terms of postponement of hip fracture by 1 month, 6 months, 1 year, and 4 years, the proportions who said they would consent to the intervention were a respective 25%, 40%, 39%, and 53%. Increasing postponement of hip fracture was significantly associated with higher proportions of consent (test for trend chi-square(1)= 20.09;P < 0.001). Logistic regression analysis found that consenting to therapy was inversely associated with age (NNT: OR, 0.83; 95% CI, 0.72-0.96; postponement of fracture: OR, 0.84; 95% CI, 0.73-0.98) and with the magnitude of benefit presented in terms of postponement of fracture. No other variables were significantly associated with consent to therapy. CONCLUSIONS: When laypersons were presented with brief information about the benefit of a hypothetical osteoporosis intervention and were then offered this therapy, their choices were sensitive to the magnitude of treatment benefit when it was presented in terms of postponement of hip fracture but not in terms of NNT. These findings suggest that it may be easier for laypersons to understand a potential treatment benefit in terms of postponement of fracture rather than NNT.

Expressing effects of osteoporosis interventions in terms of postponing of fractures.

OBJECTIVE: To estimate the effect from an osteoporosis intervention in terms of postponement of hip fractures. DESIGN: A Markov model using Nordic data on mortality and hip fracture incidence. PATIENTS: Women aged 50 years and older with increased risk of hip fracture. INTERVENTION: A hypothetical intervention that reduces the risk of hip fracture by 50%. MAIN OUTCOME MEASURES: Postponement of hip fractures--that is increase in expected fracture-free survival from osteoporosis interventions. RESULTS: A 1-year treatment would on average postpone hip fracture by 12 days if therapy were started at the age of 50 years and 23, 55, 90 or 74 days if the treatment were started at the ages of 60, 70, 80 or 90 years, respectively. For 10 years of treatment, the benefit was 146, 260, 369, 373 and 167 days, respectively. The younger the patient, the lower the risk of fracture and, consequently, the greater the benefit for those few who actually could benefit. CONCLUSIONS: The benefit in terms of average postponement of hip fractures from osteoporosis intervention was, other things being equal, greatest in women aged 70-90 years. Fracture postponement may represent an alternative to risk reductions in expressing the effect of osteoporosis interventions.

[Pharmaco-economic evaluation of drug therapy osteoporosis. A literature review]. / Farmakoøkonomiske evalueringer af medicinsk behandling af osteoporose. En litteraturoversigt.

INTRODUCTION: Interventions against osteoporosis may reduce the incidence of fractures in patients and costs to society, but they also incur additional expenditure and thus call for economic evaluation. The aim of this paper was to evaluate existing literature by applying cost-effectiveness (CEA) and cost-utility analyses (CUA) to pharmacological treatment of osteoporosis. MATERIAL AND METHODS: MEDLINE and the reference lists of relevant papers were searched to identify original papers on the subject. Studies were included if they were peer reviewed, written in English or a Scandinavian language, and reported CEA or CUA for a specified pharmacological intervention. RESULTS: Of the 37 identified studies, 16 met the inclusion criteria (ten CUA and six CEA), and 21 studies were excluded. Of the studies examined, 13 studies concerned hormone replacement therapy (HRT), four bisphosphonate, four calcitonin, and four calcium supplementation and/or vitamin D treatment. All were based on simulations of the long-term effects of the intervention with respect to cost and effect. However, the studies varied widely in patient selection and assumptions about duration and effectiveness of intervention, assessment of quality of life, and mortality following hip fracture. DISCUSSION: The published studies rely on limited empirical data as regards the effect of treatment, costs, and adverse effects. Several, however, indicate that some interventions may be cost-effective in high-risk groups.