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Background: Executing structured medication reviews (SMRs) in primary care to optimize drug treatment is considered standard care of community pharmacists in the Netherlands. Patients with Parkinson's disease (PD) often face complex drug regimens for their symptomatic treatment and might, therefore, benefit from an SMR. However, previously, no effect of an SMR on quality of life in PD was found. In trying to improve the case management of PD, it is interesting to understand if and to what extent SMRs in PD patients are of added value in the pharmacist's opinion and what are assumed facilitating and hindering factors., Objectives: To analyse the process of executing SMRs in PD patients from a community pharmacist's point of view., Design: A cross-sectional, qualitative study was performed, consisting of face-to-face semi-structured in-depth interviews., Methods: The interviews were conducted with community pharmacists who executed at least one SMR in PD, till data saturation was reached. Interviews were transcribed verbatim, coded and analysed thematically using an iterative approach., Results: Thirteen pharmacists were interviewed. SMRs in PD were considered of added value, especially regarding patient contact and bonding, individualized care and its possible effect in the future, although PD treatment is found already well monitored in secondary care. Major constraints were time, logistics and collaboration with medical specialists., Conclusion: Although community pharmacist-led SMRs are time-consuming and sometimes logistically challenging, they are of added value in primary care in general, and also in PD, of which treatment occurs mainly in secondary care. It emphasizes the pharmacist's role in PD treatment and might tackle future drug-related issues. Improvements concern multidisciplinary collaboration for optimized SMR execution and results., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: Drug therapy is important for controlling symptoms in Parkinson's disease (PD). However, it often results in complex medication regimens and could easily lead to drug related problems (DRP), suboptimal adherence and reduced treatment efficacy. A structured medication review (SMR) could address these issues and optimize therapy, although little is known about clinical effects in PD patients., Objective: To analyze whether an SMR improves quality of life (QoL) in PD., Methods: In this multicenter randomized controlled trial, half of the 202 PD patients with polypharmacy received a community pharmacist-led SMR. The control group received usual care. Assessments at baseline, and after three and six months comprised six validated questionnaires. Primary outcome was PD specific QoL [(PDQ-39; range 0 (best QoL) - 100 (worst QoL)]. Secondary outcomes were disability score, non-motor symptoms, general health status, and personal care giver's QoL. Furthermore, DRPs, proposed interventions, and implemented modifications in medication schedules were analyzed., Results: No improvement in QoL was seen six months after an SMR, with a non-significant treatment effect difference of 2.09 (-0.63;4.80) in favor of the control group. No differences were found in secondary outcomes. In total, 260 potential DRPs were identified (2.6 (±1.8) per patient), of which 62% led to drug therapy optimization., Conclusion: In the current setting, a community pharmacist-led SMR did not improve QoL in PD patients, nor improved other pre-specified outcomes.

Prescriber adherence to guideline-recommended medication in patients with heart failure (HF) in clinical practice is suboptimal. We analyzed how evolving guideline recommendations influenced medication profiles after a first HF hospitalization. We extracted medication profiles from the Dutch PHARMO Database Network for 22,476 patients with a diagnosis of HF at hospital discharge between 2001 and 2015. The percentage of patients prescribed the combination of a beta-blocker (BB) and an angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) increased from 24 to approximately 45% within this 15-year period. The percentage of patients who also used a mineralocorticoid-receptor antagonist (MRA) reached approximately 20%. The probability of being prescribed these combinations decreased with increasing age. As a consequence of the policy change in the ESC guideline 2001, the use of BB increased from less than 40% in 2001 to about 70% by 2015. The percentage of patients prescribed an ACEI and/or an ARB, an MRA, or a diuretic was about stable, at respectively 63%, 37%, and 82%. Although the 2012 ESC guideline also advised MRA in the New York Heart Association (NYHA) class II, there was no increase in MRA prescriptions. Compliance with the ESC guidelines varied for the individual recommendations. Remarkably, there was no significant increase in MRA prescriptions. At the same time, developments were demonstrated, which were not instigated by the guidelines, like the shift from ACEI to ARB. Although the exact HF classification of our patients was unknown, given a relatively stable case mix, our data provide insight into "real-world" pharmacological management.

Between 2006 and 2010, six population based case-control studies were conducted as part of the European research-project DRUID (DRiving Under the Influence of Drugs, alcohol and medicines). The aim of these case-control studies was to calculate odds ratios indicating the relative risk of serious injury in car crashes. The calculated odds ratios in these studies showed large variations, despite the use of uniform guidelines for the study designs. The main objective of the present article is to provide insight into the presence of random and systematic errors in the six DRUID case-control studies. Relevant information was gathered from the DRUID-reports for eleven indicators for errors. The results showed that differences between the odds ratios in the DRUID case-control studies may indeed be (partially) explained by random and systematic errors. Selection bias and errors due to small sample sizes and cell counts were the most frequently observed errors in the six DRUID case-control studies. Therefore, it is recommended that epidemiological studies that assess the risk of psychoactive substances in traffic pay specific attention to avoid these potential sources of random and systematic errors. The list of indicators that was identified in this study is useful both as guidance for systematic reviews and meta-analyses and for future epidemiological studies in the field of driving under the influence to minimize sources of errors already at the start of the study., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients., Methods: A crossover, placebo-controlled clinical trial was conducted in 10 patients. After administration of either a single dose of fluoxetine (20 mg) or a placebo, muscle activation of the lower arm was measured during maximum (isometric) force of the musculus flexor carpi radialis and musculus extensor carpi radialis. Delay times, grip strength, and Motricity Index were measured to assess functional ability., Results: After fluoxetine intake, a significant increase in activation was found in both agonist and antagonist muscles of the paretic arm (P < 0.05). This increase did not influence the motor function., Conclusions: In this pilot study, it was found that fluoxetine influences motor output in chronic stroke patients. Therefore, fluoxetine may influence motor recovery after stroke. Additional studies have to be conducted to explore the effects of fluoxetine on motor recovery after stroke.

Objectives: Allopurinol is a uric acid lowering drug used in the treatment of gout and the prevention of tumor lysis syndrome. Allopurinol and its active metabolite oxipurinol inhibit xanthine oxidase, which forms uric acid from xanthine and hypoxanthine. Therapeutic drug monitoring is an important option for evaluation and optimization of allopurinol treatment in case of renal impairment, interaction with uricosuric drugs or to verify patient adherence. In this study we developed and validated a simple quantitative assay using reverse phased high-performance liquid chromatography (HPLC) with UV-detection as a method for quantification of allopurinol and oxipurinol in human serum in the presence of different frequently used drugs., Methods: The HPLC-UV method uses a mobile phase consisting of sodium acetate (0.02 M; pH 4.5), at a flow rate of 1.0 mL/min. Allopurinol and oxipurinol are detected by UV-absorption at 254 nm with a retention time of 9.9 min for oxipurinol and 12.3 min for allopurinol. Aciclovir is used as internal standard., Results: Validation showed for allopurinol lower and upper limits of quantification of 0.5 and 10mg/L and for oxipurinol 1 and 40 mg/L, respectively. The assay was linear over the concentration range of 0.5-10mg/L (allopurinol) and 1-40 mg/L (oxipurinol). Intra- and inter-day precision showed coefficients of variation <15% over the complete concentration range; accuracy was within 5% for allopurinol and oxipurinol. Endogenous purine-like compounds were separated from allopurinol, oxipurinol and aciclovir with a resolution factor >1.5. Exogenous purine-like compounds and co-medication frequently used by gout patients did not hinder the analysis due to the dichloromethane washing step or to low UV-absorpion at 253 nm. Serum levels of 66 patients prescribed allopurinol 300 mg/day were determined using this HPLC-UV method. Measured serum allopurinol and oxipurinol concentrations in clinical practice showed large variability with a range of <0.5-4.3 mg/L for allopurinol and <1.0-39.2 mg/L for oxipurinol, respectively., Conclusion: We developed an easy-to-operate and validated HPLC-UV method for the quantification of allopurinol and oxipurinol in human serum. This method was proven to be valid for samples of gout patients frequently using concomitant medications.

Lithium is the drug that is most frequently associated with acquired nephrogenic diabetes insipidus (NDI). The exact mechanism of lithium-induced NDI in man is unknown. The aim of the present study was to investigate the kidney response to minimal and maximal stimulation of the kidney urine concentrating mechanism by measuring urine osmolality, and urine levels of cAMP and AQP-2 in urine of patients under long-term lithium treatment. Twenty patients under long-term lithium treatment were included. The kidney urinary 3',5'-cyclic adenosine monophosphate (cyclic AMP), aquaporin-2 levels and urine osmolality were determined during a situation of minimal kidney urine concentrating activity (induced by water loading) and during a situation following maximal stimulation of kidney urine concentrating activity (induced by 1-desamino-8-D-arginine-vasopressin). Patients were classified as NDI, partial NDI and non-NDI based on maximal reached urine osmolality. The partial correlation (r) between urinary cyclic AMP levels (mol/l) and urine osmolality was 0.94 (P<0.001). No significant correlation was observed between urinary aquaporin-2 levels (mol/mol creatinine) and osmolality nor between urinary cyclic AMP and aquaporin-2 levels. The rise in urinary cyclic AMP but not aquaporin-2 levels upon 1-desamino-8-D-arginine-vasopressin administration after water loading significantly differed between the three categories, decreasing with increasing NDI category. In conclusion we found that in lithium-induced kidney urine concentrating deficit in man, the cyclic AMP generation in response to 1-desamino-8-D-arginine-vasopressin administration after water loading, is impaired. It remains to be elucidated whether principal cells, G-proteins or adenylate cyclase e.g. are the major targets for the mechanism underlying lithium-induced NDI in man.