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Introduction: Polypharmacy is common in older adults with cancer and is associated with drug related problems (DRPs) and potentially inappropriate medication (PIM). We introduced a medication optimization care pathway for older adults with advanced cancer and a limited life expectancy and studied the prevalence of DRPs and PIMs as well as the adherence to medication-related recommendations and the patient satisfaction., Materials and Methods: A medication review was performed in patients aged ≥65 years with polypharmacy and a life expectancy of <24 months. Recommendations on adjustments of medication were discussed in a multidisciplinary team including a pharmacist, an oncologist, and a geriatrician. Implementation of the recommendations was left to the discretion of the oncologist. Four weeks after the implementation, the patient filled a questionnaire to assess satisfaction., Results: One hundred twenty patients were included. The mean age was 75 years and 39% were female. A mean of 12 medications was used. The median number of DRP was 6.0 per patient and median number of PIMs was 3.0 per patient. Overtreatment accounted for 26% of DRP and the most frequently involved drug classes were antihypertensive medication (22%), non-opioid analgesics (22%), and antilipemics (12%). The multidisciplinary team accepted 78% of the recommendations of the pharmacist and the oncologist implemented 54% of the recommendations. Overall, patients were satisfied or very satisfied with the intervention., Discussion: DRPs and PIMs are highly prevalent in this population and can be reduced by a multidisciplinary medication optimization intervention. Patients appreciate the medication optimization intervention and are satisfied with the intervention., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: To compare the real-world safety profile of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors between younger and older patients., Materials and Methods: All patients receiving pembrolizumab, nivolumab, atezolizumab or durvalumab between September 2016 and September 2019 at Haga Teaching Hospital, The Hague, The Netherlands were included in this retrospective study. Immune-related adverse drug reactions (irADRs) were manually retrieved from the electronic patient files. The cumulative incidence of irADRs were compared between younger (<65 years) and older (≥65 years) patients using a Pearsons Chi-square test., Results: We identified 217 patients who were treated with at least one dose of PD-(L)1 inhibitor. 58% were 65 years or older at the start of immunotherapy. 183 patients (84.3%) received monotherapy PD-(L)1 inhibitors and 34 (15.7%) received chemo-immunotherapy. A total of 278 irADRs were registered. Cutaneous irADRs (53.9%), thyroid gland disorders (20.3%), and non-infectious diarrhoea/colitis (17.5%) were the most frequently reported irADRs. The majority of the irADRs were mild to moderate and no fatal irADRs were observed. 61 (21.9%) of the irADRs needed systemic treatment, of which 19 (6.8%) required treatment with corticosteroids. 18 irADRs (6.5%) were severe and resulted in hospitalisation. The cumulative incidence of cutaneous irADRs was different between the age groups: 45.7% of the patients <65 years and in 60.0% of the patients ≥65 years (p = 0.036). No statistical difference was found in the cumulative incidence of other irADRs between the two age groups., Discussion: Advanced age is not associated with immune-related adverse drug reactions of PD-1 and PD-L1 inhibitors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The anti-IL-5 biologic reslizumab for the treatment of severe eosinophilic asthma is administered intravenously. In the current study home administration of intravenous reslizumab was evaluated in 24 patients included between 2019 (July) and 2020 (July). This is the first study to show that intravenous reslizumab can be administered safely and successfully in an outpatient setting. Notably, not all patients prefer home administration and severe asthma patients may have different needs when it comes to choosing treatment at home or in the hospital., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Medications at the end of life should be used for symptom control. Medications which potential adverse effects outweigh their expected benefits are called 'potentially inappropriate medications' (PIMs). PIMs are related with adverse drug events and reduced quality of life. In this study, we investigated to what extent PIMs are dispensed to older patients with lung cancer in the last month of life., Methods: We selected patients with lung cancer, aged 65+, diagnosed between 2009 and 2014, and who died before April 1st 2015 from the population-based Netherlands Cancer Registry (NCR). The NCR is linked to the PHARMO Database Network, that includes medications dispensed by community pharmacies in the Netherlands. The eight PIM groups were based on the OncPal Deprescribing Guideline: aspirin, dyslipidaemia medications, antihypertensives, osteoporosis medications, peptic ulcer prophylaxis, oral hypoglycaemics, vitamins and minerals., Results: Data of 7864 patients with lung cancer were analyzed. Median age was 74 year (IQR = 70-79) and 67% was male. 45% of all patients received at least one PIM in their last month of life. Taking into account all dispensed medications, patients receiving PIMs received more different medications compared to those receiving no PIMs, respectively 10 (SD = 5) vs. 3 (SD = 4) different medications (P < 0.001)., Conclusion: Almost half of the older patients with lung cancer in the Netherlands received PIMs in their last month of life. Since PIM use is associated with reduced quality of life, it is important that health care professionals continue to critically assess which medication can be discontinued at the end of life., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Non-alcoholic fatty liver or hepatic steatosis is considered the hepatic manifestation of the metabolic syndrome. Statins are often used by patients with metabolic syndrome, but their effect in steatosis is not well established., Aims: To study the association between statins and the presence of steatosis., Methods: In the population-based Rotterdam Study, 2578 subjects underwent liver ultrasonography and had prescription data available. In a cross-sectional design, we investigated the effect of current, past, and duration of statin use. Logistic regression analyses were adjusted for age, sex, and other known risk factors., Results: The prevalence of steatosis was 35.3%. We identified 631 current and 359 past statin users. In multivariable analyses, current statin use >2 years was associated with a significantly lower steatosis prevalence [OR 0.43, 95% CI 0.19-0.96]. Stratification by mean body mass index showed that this association was stronger in patients with body mass index ≥ 27.5 [OR 0.30, 95% CI 0.11-0.81 for current use >2 years], while in patients with body mass index <27.5 the association was non-significant., Conclusion: Within the Rotterdam study, in patients with body mass index ≥ 27.5 current use of statins for >2 years was associated with a lower prevalence of steatosis., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The enzyme CYP1A2 (cytochrome 1A2) is involved in the metabolism of certain drugs and caffeine, and its activity can be influenced by factors such as sex, age, and smoking. The single nucleotide polymorphism (SNP) rs762551A>C, which has also been studied for its modifying effect on cardiovascular disease, has been reported to alter enzyme activity., Objective: The objective was to study the effect of CYP1A2, sex, age, and smoking on coffee intake., Design: Within the Rotterdam Study, a population-based cohort, all coffee drinkers for whom genome-wide association data were available were selected. Because SNP rs762551 was not on the Illumina 550 platform, SNP rs2472299 was used as a proxy, with the A allele of rs762551 linked to the G allele of rs2472299. Linear regression analyses were used to determine the effect and interaction of rs2472299, sex, age, and smoking on coffee intake. Adjusted geometric means of coffee intake were calculated per genotype for the different smoking and sex strata by using multivariable general linear models. A combined analysis, with the use of a "risk score," was performed to determine the contribution of each separate factor., Results: rs2472299G>A, female sex, and nonsmoking were significantly inversely related to coffee intake. Coffee intake was lowest in nonsmoking women homozygous for rs2472299G>A (3.49 cups/d; ∼436 mL). All factors contributed almost linearly to the intake of coffee, with the highest coffee intake in smoking men without the A allele (5.32 cups/d; ∼665 mL)., Conclusion: rs2472299G>A, linked to rs762551A>C, sex, age, and smoking significantly contribute to coffee intake.

Background: The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known., Objectives: In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated., Patients/methods: In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation., Results: Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6 months., Conclusions: Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy., (© 2012 International Society on Thrombosis and Haemostasis.)

Purpose: To study if polymorphisms in genes encoding for CYP3A enzymes, that play a role in steroid hormone metabolism, affect steroid hormone serum levels and prostate cancer incidence or mortality., Methods: 3048 male participants of The Rotterdam Study were included. Prostate cancer cases and non-cases were studied for differences in baseline hormone levels with Student's t-test. General linear models were performed on different random subsets of hormone levels to study associations with genotype. Cox' proportional hazard models were used to study prostate cancer incidence and mortality among genotypes., Results: Both DHEAS sulphate as free-testosterone were significantly increased at baseline in males who developed a prostate cancer within the study period. CYP3A4 G-allele carriage was associated with lower levels of estrone sulphate (p=0.005) and higher levels of estradiol (p=0.04) compared to non-carriers. CYP3A5 A-allele carriage was associated with increased levels of estrone sulphate (p=0.02). CYP3A7 G-allele carriage was associated with the highest number of significant differences in steroid hormone levels. Carriers of the allele resulting in continued enzyme expression during adulthood had decreased levels of dehydroepiandrosterone (DHEA) sulphate (p=0.05), androstenedione (p=0.006), estrone (p=0.0001) and estrone sulphate (p=0.003) compared to mean levels of these hormones in homozygous wild type carriers. CYP3A43 genotype was not associated with any of the studied hormone levels. However, carriers of the CYP3A43 G-allele showed a significant 5-fold increase in mortality among early onset diagnosed prostate cancers., Conclusion: Increased levels of free testosterone and DHEA sulphate were associated with prostate cancer incidence along the study period. Primarily the amount of CYP3A7 expression seemed to affect steroid hormone levels. Nevertheless, testosterone, a precursor of the prostate growth and differentiation stimulating dehydrotestosterone, was not influenced by CYP3A genotype. In line with this, no significant associations were observed for CYP3A genotypes and prostate cancer incidence., (Copyright 2010 Elsevier Inc. All rights reserved.)

The objectives of this study were to determine the risk for coughing as an adverse reaction to angiotensin converting enzyme (ACE) inhibitors under everyday circumstances in a large population and to study whether this adverse effect is more common in women. A population-based case-control study was used. The study was set in the practices of 161 Dutch general practitioners (GPs), in which all consultations, morbidity, mortality, medical interventions and prescriptions were registered during 4 consecutive 3-month periods in 4 consecutive groups of 40-41 GPs. The subjects were 2436 patients with incident coughing and up to 3 controls per case were obtained (total group: 7348 controls), matched for GP and a contemporary consultation in the same 3 months. All cases and controls were 20 years or older and had no notification of respiratory infections, influenza, tuberculosis, asthma, chronic bronchitis, emphysema, congestive heart failure, sinusitis, laryngitis, haemoptysis or respiratory neoplasms during the 3-month period. The results showed that cases were 3.6 times as likely as controls to have been exposed to ACE inhibitors (95% CI: 2.4-5.5) but after adjustment for potential confounders the odds ratio was 2.5 (95% CI: 1.6-3.9). The crude odds ratio for males was 2.7 (95% CI: 1.4-5.1) and for females 4.2 (95% CI: 2.4-7.5). The adjusted odds ratio for males was 1.8 (95% CI: 0.9-3.5) and for females 2.7 (95% CI: 1.5-4.8).(ABSTRACT TRUNCATED AT 250 WORDS)