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- Linnér, Love, et al.
(författare)
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Forecasting drug utilization and expenditure : ten years of experience in Stockholm.
- 2020
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Operating under constrained budgets, payers and providers globally face challenges in enabling appropriate and sustainable access to new medicines. Among payer initiatives aiming to improve preparedness of healthcare systems for the introduction of new medicines, drug utilization and expenditure forecasting has played an increasingly important role. This study aims to describe the forecasting model used in Region Stockholm and to evaluate the accuracy of the forecasts produced over the past decade.METHODS: In this repeated cross-sectional study, we compared the predicted pharmaceutical expenditure with actual expenditure during the entire available follow-up period (2007-2018) both for overall drug utilization and for individual therapeutic groups. All analyses were based on pharmaceutical expenditure data that include medicines used in hospitals and dispensed prescription medicines for all residents of the region.RESULTS: According to the forecasts, the total pharmaceutical expenditure was estimated to increase between 2 and 8% annually. Our analyses showed that the accuracy of these forecasts varied over the years with a mean absolute error of 1.9 percentage points. Forecasts for the same year were more accurate than forecasts for the next year. The accuracy of forecasts also differed across the therapeutic areas. Factors influencing the accuracy of forecasting included the timing of the introduction of both new medicines and generics, the rate of uptake of new medicines, and sudden changes in reimbursement policies.CONCLUSIONS: Based on the analyses of all forecasting reports produced since the model was established in Stockholm in the late 2000s, we demonstrated that it is feasible to forecast pharmaceutical expenditure with a reasonable accuracy. A number of factors influencing the accuracy of forecasting were also identified. If forecasting is used to provide data for decisions on budget allocation and agreements between payers and providers, we advise to update the forecast as close as possible prior to the decision date.
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| 4. |
- Linnér, Love
(författare)
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Noradrenergic augmentation strategies in the pharmacological treatment of depression and schizophrenia : an experimental study
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The pharmacological treatment of depression and schizophrenia, two major psychiatric disorders, is largely based on modulation of central monoaminergic neurotransmission. However, currently available pharmacological treatment alternatives possess a relatively modest clinical efficacy, making them less than optimal. The present series of studies, using in vivo electrophysiological, biochemical and behavioral techniques in rats, aim at the disclosure of mechanisms whereby an augmented clinical efficacy of antidepressant, as well as antipsychotic, drugs may be achieved. Pindolol, a partial beta-adrenoceptor agonist with affinity for the serotonin (5-HT) ]A receptor, has been claimed to shorten the clinical onset of action of selective serotonin reuptake inhibitors (SSRIs); an effect suggested to result from an antagonistic action of pindolol on somatodendritic 5-HT1A autoreceptors, reversing the acute, inhibitory, effect of SSRIs on serotonergic neuronal activity. However, upon systemic administration, pindolol, in contrast to the selective 5-HT1A receptor antagonist WAY 100635, was unable to reverse the inhibitory effect of an SSRI on 5-HT neuronal activity. This observation, in conjunction with other data from our laboratory, rather indicates that pindolol exerts a weak agonistic activity on sontatodendritic 5-HT1A autoreceptors and thus may shorten the delayed onset of action of SSRIs by a mechanism unrelated to 5-HT1A receptor blockage. In other experiments, repeated treatment with a noradrenaline reuptake inhibitor (NRI), was found to cause a gradual increase in noradrenaline nerve-terminal output and a partial recovery of the initially suppressed noradrenergic electrophysiological activity during the course of the treatment, consonant with a partial desensitization of the presynaptic inhibitory feedback mechanism. Administration of a low dose of an alpha2-adrenoceptor antagonist enhanced noradrenaline neuronal activity, as well as nerve-terminal. release, most markedly in chronically, but also acutely, treated animals; tentatively indicating an advantageous effect of this drug combination in the treatment of at least some forms of depression. Modulation of central serotonergic function is thought to mediate the clinical action of several classes of antidepressant drugs, and previous data demonstrate a central noradrenergic regulation of midbrain scrotonergic neurons. We have now observed that acute administration of die highly selective NRI reboxetine increases the firing rate of serotonin neurons in the dorsal raphe nucleus, which, in turn, results in an enhanced cortical output of serotonin; effects that may have bearing on the clinical action of selective NRls. Analogous studies of the effects of NRIs on the function of the mesolimbocortical dopamine system revealed several effects. Thus, acute administration of reboxetine increased burst firing, but not basal firing rate, of dopamine neurons in the ventral tegmental area and concomitantly enhanced doparmine output in the prefrontal cortex, but not in the nucleus accumbens, This effect of reboxetine on cortical dopamine release is similar to that caused by alpha2-adrenoceptor antagonists as well as most atypical antipsychotic: drugs. Previous observations have shown that concomitant treatment with an cc, adrenoceptor antagonist my markedly enhance the effect of a dopamine D2 receptor antagonist, i.e. a classical antipsychotic drug, on prefrontal dopamine output as well as in the conditioned avoidance response (CAR) test, a preclinical test of antipsychotic efficacy with high predictive validity, supporting the observed advantageous clinical antipsychotic effect of this drug combination. Given the similar effects of alpha2-adrenoceptor blockage and noradrenaline reuptake inhibition on cortical dopamine function, we investigated the effect of reboxetine in the same experimental paradigm. Pretreatment with reboxetine significantly enhanced the effect of the D 2 receptor antagonist on cortical dopamine output as well as in the CAR test, without affecting catalepsy scores. Our data thus indicate that noradrenaline reuptake inhibition may augment the clinical effect of classical antipsychotic drugs in the treatment of schizophrenia, tentatively with particular regard to negative and cognitive symptoms.
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| 5. |
- Linner, Love, et al.
(författare)
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Reboxetine modulates the firing pattern of dopamine cells in the ventral tegmental area and selectively increases dopamine availability in the prefrontal cortex
- 2001
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - 0022-3565 .- 1521-0103. ; 297:2, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Central dopaminergic neurons have been suggested to be involved in the pathophysiology of several psychiatric disorders, including depression, and appear to be modulated by noradrenergic activity both at the nerve terminal level and at the somatodendritic level. In recent years reboxetine, a selective noradrenaline reuptake inhibitor that differs from tricyclic anti-depressants by its low affinity for muscarinic, cholinergic and α1-adrenergic receptors, has been introduced clinically. In the present study the effect of reboxetine on the function of the mesolimbocortical dopamine system was investigated by means of single cell recording and microdialysis in rats following administration of reboxetine in doses that appear to yield clinically relevant plasma concentrations. Reboxetine (0.625-20 mg/kg intravenously) induced an increase in burst firing, but not in average firing frequency of dopamine (DA) cells in the ventral tegmental area (VTA). Moreover, reboxetine (0.15-13.5 mg/kg intraperitoneally) caused a significantly enhanced DA output in the medial prefrontal cortex, whereas no effect was observed in the nucleus accumbens. Local administration of reboxetine (333 μM, 60 min), by means of reversed microdialysis into these brain regions, caused a significant increase in DA output in both brain regions. However, local administration of reboxetine into the VTA (333 μM, 60 min) did not affect DA availability in these terminal areas. Our results imply that clinical treatment with reboxetine may result in facilitation of both prefrontal DA output and the excitability of VTA DA neurons, effects that may contribute to its antidepressant action, especially on drive and motivation.
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- Loikas, Desirée, et al.
(författare)
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Post-stroke epilepsy and antiepileptic drug use in men and women
- 2021
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 129:2, s. 148-157
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based recommendations for choice of antiepileptic drug (AED) in post-stroke epilepsy (PSE) are lacking. The aim of this study was to describe the use and persistence of AEDs when initiating treatment in men and women with PSE. An observational study based on individual-level patient data from a regional health care register in Stockholm, Sweden, was conducted. Adults (≥18 years) with a stroke diagnosis 2012-2016, a dispensed prescription of any AED within two years after the stroke, and with an epilepsy-related diagnosis were identified. Multinomial logistic regression and logistic regression was used to identify factors associated with choice of AED and discontinuation within 90 days, respectively. Of 9,652 men and 9,844 women with a stroke diagnosis, 287 men and 273 women had PSE and were dispensed AED. More than 60% of both men and women with PSE were treated with levetiracetam. Carbamazepine was the second most common drug followed by lamotrigine and valproic acid. There were significant differences in AED choice depending on for instance sex, age and renal impairment. Levetiracetam had the highest persistence in both men and women. Choice of AED, oral anticoagulant use and percutaneous endoscopic gastrostomy (PEG) showed an association with the persistence to therapy. We conclude that in both men and women with PSE, levetiracetam was the most used AED for initiation of treatment and also had the highest persistence.
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| 7. |
- Nilsson, Fredrik O. L., et al.
(författare)
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Cost-effectiveness analysis of newer anticholinergic drugs for urinary incontinence vs oxybutynin and no treatment using data on persistence from the Swedish prescribed drug registry
- 2012
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Ingår i: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 110:2, s. 240-246
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To analyse the cost-effectiveness of newer anticholinergic drugs in relation to oxybutynin immediate release (IR) and no treatment for patients with urgency urinary incontinence. PATIENTS AND METHODS A decision analytic model was constructed. Results were collected from randomized trials and combined with registry data on persistence of medicine use and estimated number of severe adverse events. The setting corresponds to Swedish clinical practice. The costs and effects of the treatment options were analysed over a period of 1 year. Costs included drug costs, treatment costs and costs for pad use. Patients' utilities were based on treatment effect and the lack or presence of adverse events. RESULTS No treatment was the least costly treatment but also resulted in the fewest number of quality adjusted life years (QALYs). Treatment with newer anticholinergic drug medications is the most costly option but also the most efficient treatment. Sensitivity analyses showed that the results were robust. Treatment with newer anticholinergics resulted in a cost per QALY gained of (sic)21 045 compared with no treatment and no effect and (sic)65 435 compared with no treatment and placebo effect. Compared with oxybutynin IR, the cost per QALY gained was (sic)37 119. These calculations are based on relatively low pad costs, resulting in higher costs per QALY for the original drugs. CONCLUSIONS The newer anticholinergic medications are likely to be cost effective in relation to oxybutynin IR. The cost-effectiveness of the newer anticholinergics compared with no treatment depends on assumptions of the effect of no treatment, the severity of the treated condition and the treated individual's risk of adverse events. Treatment is less likely to be cost effective for elderly persons or for persons otherwise at higher risk for adverse events.
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