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BACKGROUND: Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. AIMS: To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. METHOD: The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. RESULTS: Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. CONCLUSIONS: A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour

Про оцінку напружено-деформованого стану конвеєрної стрічки на дузі ковзання

Работа посвящена расширению сферы применения техники Л. Прандтля на решение задачи о взаимодействии конвейерной ленты и нефутерованного барабана. Получено решение задачи Ламе с соответствующими граничными условиями, что позволило выяснить характер деформаций на дуге скольжения. Приведены графики деформаций и соответствующих им напряжений.The paper is devoted to expand L. Prandtl technique to contact the conveyor belt with rigid drum. The Lamb task solving with corresponding boundary condition allow explaining the deflection nature in slide arch drum. The deflections and corresponding stresses graphics are demonstrated

Less discontinuation of ADHD drug use since the availability of long-acting ADHD medication in children, adolescents and adults under the age of 45 years in the Netherlands

Treatment options for ADHD in the Netherlands have increased with the introduction of the extended-release formulations of methylphenidate (MPH ER, Concerta®) in 2003 and atomoxetine (ATX, Strattera®) in 2005, but data on the effect on drug usage patterns are scarce. The objective of the present study was to describe changes in the patterns of ADHD medication use and determinants thereof among children, adolescents and adults (<45 years) starting ADHD medication since the introduction of MPH ER and ATX. Data were obtained from Dutch community pharmacies as collected by the Foundation for Pharmaceutical Statistics, covering 97% of all dispenses for prescription medicines to outpatients in the Netherlands. Usage patterns (continuation, discontinuation, switching and addition) of ADHD drugs were evaluated at 3, 6 and 12 months after initiation for three separate time cohorts (patients starting ADHD medication in Jan-Dec 2002, Jan 2003–June 2004, respectively July 2004–Dec 2005). It was found that between 2002 and 2006, most ADHD drug users were initiated on methylphenidate IR. Discontinuation of any ADHD drug treatment decreased over time partly in favour of switching and addition. Discontinuation at 3 months decreased from around 33% to around 25%, at 6 months from less than 50% to almost 35%, and at 12 months from just fewer than 60% to less than 45%. Discontinuation was higher among females and in adults >18 years. After the introduction of MPH ER and ATX (time cohort III), 16.5% of the incident ADHD drug users switched their medication and almost 9% added an ADHD drug to the prior ADHD drug. In conclusion, discontinuation of incident ADHD drug use is high after 3, 6 and 12 months. During the study period, the incidence of discontinuation decreased because of the availability of extended-release methylphenidate and atomoxetine

Post-approval quality-related regulatory actions for biopharmaceuticals approved in the European Union and the United States between 1995 and 2019

The quality of biopharmaceuticals is carefully monitored by manufacturers and regulators to ensure safety and efficacy throughout the entire product life cycle. Quality defects can lead to post-approval regulatory actions (RAs) to inform healthcare professionals (HCPs). The present study identified quality-related RAs for biopharmaceuticals approved in the European Union and United States between 1995 and 2019. Quality-related RAs were issued due to various quality defects and required different actions by HCPs. The quality defects were not identified due to a negative impact on efficacy and/or safety, which is reassuring. The findings reflect the capability of the stringent regulatory system and quality control to capture and counter various quality defects before the affected product and batches can harm patients

Guidance by physicians and pharmacists during antidepressant therapy:Patients' needs and suggestions for improvement

Background: Guidance of patients treated with antidepressants is paramount for successful therapy. The aim was to assess patients' needs and suggestions for improvement of guidance by physicians and pharmacists during second generation antidepressant (SGA) therapy. Methods: Five focus group discussions were held with a total of 34 patients using an SGA. The discussions were conducted flexibly and responsively using a semi-structured topic list. All focus group discussions were video-recorded and transcripts were analyzed using ATLAS.ti for coding, thematic and open analysis. Results: Participants stated they were in need of better guidance. They suggested improving content of information during decisional moments, patient-health care professional communication and communication between health care professionals, and finally, organization of guidance. Barriers to achieving improved guidance were cited. Conclusions: Content, communication and organization of guidance are pivotal for achieving optimal guidance. Participants mentioned their current experienced guidance had limitations and brought up solutions for improvement. A next step would be to discuss the suggested solutions with health care professionals to assess their views and to discuss the possibility for implementation. After implementation, future studies could be aimed at determination of its impact on patients' treatment efficacy, quality of life, treatment satisfaction and healthcare costs

Impulse control disorders associated with dopaminergic drugs: A disproportionality analysis using vigibase

BACKGROUND: Dopamine receptor agonist drugs, which are used, for example, to treat Parkinson's disease (PD), increase the risk for impulse control disorders (ICDs), potentially resulting in devastating psychosocial consequences. It is unknown whether other drugs with dopaminergic properties also increase the risk for ICDs. This study assesses the disproportionality of reporting ICDs between drugs with dopaminergic properties and selected non-dopaminergic drugs. METHODS: A case/non-case disproportionality analysis was performed, using data from VigiBase (1968-2020). Reports on ICDs as suspected adverse drug reactions (ADRs) were cases (n=852), and those with ADRs other than ICDs were non-cases (n=281,720). Relative reporting frequencies were expressed as adjusted reporting odds ratios (aRORs). Within the dopamine receptor agonists, the relationship between reporting odds ratios and dopamine receptor occupancy was explored. RESULTS: A high disproportionality was found for reporting ICDs for all dopaminergic drugs (aROR 20.4 [95% CI 17.4-24.1]) compared to non-dopaminergic drugs. In pharmacotherapeutic subgroups, a high disproportionality was found for primary dopaminergic agents used in PD (aROR 52.1 [95% CI 44.1-61.5]), and to a lesser extent for ADHD psychostimulants and antidepressants (aROR 5.8 [95% 4.1-8.3] and aROR 3.9 [95% CI 2.9-5.6], respectively). There was no difference in reporting by consumers and healthcare professionals. The highest disproportionality was found for the dopamine receptor agonists pramipexole and ropinirole. CONCLUSIONS: A signal of disproportion in ICD occurrence was found among all investigated drugs with dopaminergic properties, highlighting the importance of counselling and monitoring for ICDs when prescribing dopaminergic drugs

Nature and timing of post-approval manufacturing changes of tumour necrosis factor α inhibitor products: A 20-year follow-up study of originators and biosimilars

The manufacturing of biopharmaceuticals is complex, and minor changes in the process may affect quality attributes (QAs) that may, in turn, impact clinical outcomes. Regulatory documents from the European Medicines Agency were used to characterize two aspects, nature and timing, of post-approval MCs for originators and biosimilars TNF-α inhibitors that were on the European market up to May 2021. The nature of MCs was evaluated in two ways: (1) the type of MCs related to the drug substance (DS) or drug product (DP), classified as manufacturing, quality control, composition, packaging, or stability with various subtypes; and (2) the risk level according to the potential impact of the MCs on QAs, classified as low, medium, or high. Timing was defined as the date of the regulatory decision on the MC in relation to the approval date. We identified 801 post-approval MCs implemented to originators (mean: 137, range: 112-175) and biosimilars (mean: 30, range: 0-133). Most of implemented MCs for originators and biosimilars were classified as low and medium risk (88.1%), and a small fraction were considered high-risk (11.9%). The average incidence rates were comparable for both originators and biosimilars (7.0/year for MCs, 0.8/year for high-risk MCs). In 20% of MCs introduced to biosimilars, the DP manufacturing site was involved (9% for originators). In contrast, 16% of MCs introduced to originators were related to the DS manufacturing processes (only 7% for biosimilars). In conclusion, while the overall MC incidence rate and the risk level of MCs was not substantially different between TNF-α inhibitor products, we observed some differences in a few types of MCs related to DS manufacturing process and DP manufacturing site between originators and biosimilars. As far as our data shows there is no reasons to assume that post-approval MCs will lead to differences between TNF-α-i originators and biosimilars in clinical practice

Аліментні обов'язки інших членів сім'ї та родичів

Виявлено проблеми у врегулюванні аліментних обов’язків інших членів сім’ї та родичів, вироблено рекомендації щодо їх вирішення. Проаналізовано специфіку правового регулювання аліментних зобов’язань зазначених суб’єктів, сімейне законодавство та міжнародний досвід. Ключові слова: аліментні обов’язки, правове регулювання, сімейне законодавство.Выявлены проблемы в урегулировании алиментных обязанностей других членов семьи и родственников, выработаны рекомендации по их решению. Проанализирована специфика правового регулирования алиментных обязательств указанных субъектов, семейное законодательство и международный опыт. Ключевые слова: алиментные обязанности, правовое регулирование, семейное законодавствоThis article is dedicated to identifying problems in the regulation of the alimentary obligations of other family members and relatives, and to making recommendations and proposing solutions. Studing the specificity of the legal regulation of alimentary obligations of these entities, analysing the current family law and international experience are very important. Key words: alimentary obligations, legal regulation, family law

Association between the magnitude of intravenous busulfan exposure and development of hepatic veno-occlusive disease in children and young adults undergoing myeloablative allogeneic hematopoietic cell transplantation

BACKGROUND Intravenous busulfan is widely used as part of myeloablative conditioning regimens in children and young adults undergoing allogeneic hematopoietic cell transplantation (HCT). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious clinical problem observed with busulfan-based conditioning HCT. The development of VOD/SOS may be associated with busulfan exposure. Getting more insight in the association between busulfan exposure and the development of VOD/SOS enables further optimization of dosing and treatment strategies. OBJECTIVE The objective of this study was to assess the association between the magnitude of busulfan exposure and the occurrence of VOD/SOS in children and young adults undergoing myeloablative conditioning with a busulfan-containing regimen prior to allogeneic HCT. STUDY DESIGN In this observational study we included all patients who received an allogeneic HCT with intravenous busulfan as part of the conditioning regimen at 15 pediatric transplantation centers between 2000 and 2015. The endpoint was the development of VOD/SOS. The magnitude of busulfan exposure was estimated using non-linear mixed effect modelling and expressed as the maximal concentration (Cmax; day 1 and day 1-4 Cmax), cumulative area under the curve (AUC; day 1, highest 1-day AUC in 4 days, and 4-day cumulative AUC), cumulative time above a concentration of 300 µg/L, and clearance on day 1. RESULTS A total of 88 out of 697 patients (12.6%) developed VOD/SOS. The number of alkylators in the conditioning regimen was a strong effect modifier, therefore, we stratified the regression analysis for the number of alkylators. For patients receiving only busulfan as one alkylator (36.3%, n = 253), cumulative busulfan exposure (>78 mg*h/L) was associated with increased VOD/SOS risk (12.6% vs. 4.7%; odds ratio (OR) = 2.95, 95% CI 1.13-7.66). For individuals receiving busulfan with one or two additional alkylators (63.7%, n = 444), cumulative busulfan exposure (≤78 and >78 mg*h/L) did not further increase the risk of VOD/SOS (15.4% vs. 15.2%; OR = 1.03, 95% CI 0.61-1.75). CONCLUSION The effect of the magnitude of busulfan exposure on VOD/SOS risk in children and young adults undergoing HCT is dependent on the number of alkylators. In patients receiving busulfan as the only alkylator, higher cumulative busulfan exposure increased the risk of VOD/SOS, whereas in those receiving multiple alkylators, the magnitude of busulfan exposure did not further increase this risk