PIH22 Cost-Effectiveness Of Cyp2d6 Genotyping In Older Depressed Patients, Starting With Nortriptyline Therapy

Objectives: Genotyping for the cytochrome P450-2D6 has the potency to predict differences in metabolism of nortriptyline. This information could optimize treatment. We explored if possible benefits could outweigh genotyping costs for Dutch depressed patients in clinical psychiatry. Methods: First, a decision-tree was created to model the first weeks of nortriptyline therapy. In the model, costs of hospitalization, therapeutic drug monitoring, and drug costs were captured. Based on the patients genetics, patients were distributed among three health states: correctly, sub-, or supra-therapeutically dosed. Utilities for each of these health states and at different points in time were obtained from an expert opinion (nine clinicians). Second, an improvement in sub or supra-therapeutically dosed patients to correctly dosed patients, was simulated, assuming genotyping would prevent under or overdosing. In the base case the improvement was 36%. In addition, we assumed genotyping could reduce hospitalization days with a maximum of 3.7 days (average: 28.6 days). Results from the model without genotyping were compared with the genotyping model. In a scenario analyses we varied the effects of genotyping to reach cost-effectiveness at € 20 000/quality adjusted life year (QALY) or € 50 000/ QALY. In a univariate sensitivity analysis, effects of lowering genotyping costs were examined. A probabilistic sensitivity analysis (PSA) was performed to investigate influence of parameter uncertainty. Results: In the base case, the incremental cost-effectiveness ratio (ICER) was € 32 697/QALY. For an ICER of € 20 000/QALY, a genotyping facilitated improvement of 45% was needed and for € 50 000/QALY this was 27%. Lowering the genotype price to € 162 made genotyping cost-saving. Results of the PSA indicated a probability of 0.95 for a willingness-to-pay threshold of € 46000/ QALY. Conclusions: Genotyping could be cost-effective and even be cost-saving when genotyping costs drops. However, there is a need for more clinical evidence to support assumptions made in this model

Real-world effects of antibiotic treatment on acute COPD exacerbations in outpatients: a cohort study under the PharmLines initiative

Background: Although antibiotic treatment is recommended for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), its value in real-world settings is still controversial. Objectives: This study aimed to evaluate the short- and long-term effects of antibiotic treatment on AECOPD outpatients. Methods: A cohort study was conducted under the PharmLines Initiative. We included participants with a first recorded diagnosis of COPD who received systemic glucocorticoid treatment for an AECOPD episode. The exposed and reference groups were defined based on any antibiotic prescription during the AECOPD treatment. The short-term outcome was AECOPD treatment failure within 14-30 days after the index date. The long-term outcome was time to the next exacerbation. Adjustment for confounding was made using propensity scores. Results: Of the 1,105 AECOPD patients, antibiotics were prescribed to 518 patients (46.9%) while 587 patients (53.1%) received no antibiotics. The overall antibiotic use was associated with a relative risk reduction of AECOPD treatment failure by 37% compared with the reference group (adjusted odds ratio [aOR] 0.63 [95% CI: 0.40-0.99]). Protective effects were similar for doxycycline, macrolides, and co-amoxiclav, although only the effect of doxycycline was statistically significant (aOR 0.53 [95% CI: 0.28-0.99]). No protective effect was seen for amoxicillin (aOR 1.49 [95% CI: 0.78-2.84]). The risk of and time to the next exacerbation was similar for both groups. Conclusion: Overall, antibiotic treatment, notably with doxycycline, supplementing systemic glucocorticoids reduces short-term AECOPD treatment failure in real-world outpatient settings. No long-term beneficial effects of antibiotic treatment on AECOPD were found for the prevention of subsequent exacerbations.Clinical epidemiolog

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia

INTRODUCTION: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. AIMS: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. METHODS: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. RESULTS: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. CONCLUSION: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia

Sex disparities in the effect of statins on lipid parameters:The PharmLines Initiative

Real-world evidence on a potential statin effect modification by sex is inconclusive, especially for the primary prevention of cardiovascular disease (CVD). We aimed to quantify the differences in the effect of statins on lipid parameters between men and women. The PharmLines Initiative linked the Lifelines Cohort Study and the IADB.nl prescription database. This database covers a representative population from the Netherlands. We selected participants aged ≥40 years at the index date: the date of the first prescription of any statin monotherapy in the study period 2006 to 2017. Multivariate regression modeling was used to compare the difference of the mean percentage change of lipid parameters (% mean difference [MD]) from baseline to follow-up measurement between the sexes. Out of 5366 statin users from approximately 50,000 participants available in the final linked database, 685 were statin initiators. At baseline, women had significantly higher levels of mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) than men (all P values <.01). At follow-up, women had a significantly higher mean percentage change of HDL-C compared to men (adjusted % MD 5.59, 95% confidence interval [CI] 2.42-8.75, P < .01). There was no significant sex difference in other parameters, nor in the proportion of men and women who achieved LDL-C ≤2.5 mmol/L. Statins appear to have a greater effect on increasing HDL-C levels in women than men while showing similar effect on other lipid parameters in both sexes. Men should not be treated differently than women

Association of Polymorphisms of Serotonin Transporter (5HTTLPR) and 5-HT2C Receptor Genes with Criminal Behavior in Russian Criminal Offenders

Background: Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of ag

Sex disparities in the effect of statins on lipid parameters: The PharmLines Initiative

Real-world evidence on a potential statin effect modification by sex is inconclusive, especially for the primary prevention of cardiovascular disease (CVD). We aimed to quantify the differences in the effect of statins on lipid parameters between men and women. The PharmLines Initiative linked the Lifelines Cohort Study and the IADB.nl prescription database. This database covers a representative population from the Netherlands. We selected participants aged ≥40years at the index date: The date of the first prescription of any statin monotherapy in the study period 2006 to 2017. Multivariate regression modeling was used to compare the difference of the mean percentage change of lipid parameters (% mean difference [MD]) from baseline to follow-up measurement between the sexes. Out of 5366 statin users from approximately 50,000 participants available in the final linked database, 685 were statin initiators. At baseline, women had significantly higher levels of mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and highdensity lipoprotein cholesterol (HDL-C) than men (all P values <.01). At follow-up, women had a significantly higher mean percentage change of HDL-C compared to men (adjusted%MD 5.59, 95% confidence interval [CI] 2.42-8.75, P<.01). There was no significant sex difference in other parameters, nor in the proportion of men and women who achieved LDL-C ≤2.5mmol/L. Statins appear to have a greater effect on increasing HDL-C levels in women than men while showing similar effect on other lipid parameters in both sexes. Men should not be treated differently than women

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia

Introduction: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. Aims: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. Methods: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. Results: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. Conclusion: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia