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Objective: Described here is the development of an ultrasound matrix transducer prototype for high-frame-rate 3-D intra-cardiac echocardiography., Methods: The matrix array consists of 16 × 18 lead zirconate titanate elements with a pitch of 160 µm × 160 µm built on top of an application-specific integrated circuit that generates transmission signals and digitizes the received signals. To reduce the number of cables in the catheter to a feasible number, we implement subarray beamforming and digitization in receive and use a combination of time-division multiplexing and pulse amplitude modulation data transmission, achieving an 18-fold reduction. The proposed imaging scheme employs seven fan-shaped diverging transmit beams operating at a pulse repetition frequency of 7.7 kHz to obtain a high frame rate. The performance of the prototype is characterized, and its functionality is fully verified., Results: The transducer exhibits a transmit efficiency of 28 Pa/V at 5 cm per element and a bandwidth of 60% in transmission. In receive, a dynamic range of 80 dB is measured with a minimum detectable pressure of 10 Pa per element. The element yield of the prototype is 98%, indicating the efficacy of the manufacturing process. The transducer is capable of imaging at a frame rate of up to 1000 volumes/s and is intended to cover a volume of 70° × 70° × 10 cm., Conclusion: These advanced imaging capabilities have the potential to support complex interventional procedures and enable full-volumetric flow, tissue, and electromechanical wave tracking in the heart., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Anticholinergic drugs put elderly patients at a higher risk for falls, cognitive decline, and delirium as well as peripheral adverse reactions like dry mouth or constipation. Prescribers are often unaware of the drug-based anticholinergic burden (ACB) of their patients. This study aimed to develop an anticholinergic burden score for drugs licensed in Germany to be used by clinicians at prescribing level., Methods: A systematic literature search in pubmed assessed previously published ACB tools. Quantitative grading scores were extracted, reduced to drugs available in Germany, and reevaluated by expert discussion. Drugs were scored as having no, weak, moderate, or strong anticholinergic effects. Further drugs were identified in clinical routine and included as well., Results: The literature search identified 692 different drugs, with 548 drugs available in Germany. After exclusion of drugs due to no systemic effect or scoring of drug combinations (n = 67) and evaluation of 26 additional identified drugs in clinical routine, 504 drugs were scored. Of those, 356 drugs were categorised as having no, 104 drugs were scored as weak, 18 as moderate and 29 as having strong anticholinergic effects., Conclusions: The newly created ACB score for drugs authorized in Germany can be used in daily clinical practice to reduce potentially inappropriate medications for elderly patients. Further clinical studies investigating its effect on reducing anticholinergic side effects are necessary for validation.

Objectives: The aim was to explore the views of professional stakeholders and healthcare professionals (HCPs) on the linkage of UK National Health Service (NHS) data for paediatric pharmacovigilance purposes and to make recommendations for such a system., Methods: A mixed methods approach including a literature review, interviews, focus groups and a three-round Delphi survey with HCPs in Scotland was followed by a triangulation process using a systematic protocol. The survey was structured using the Theoretical Domains Framework of behaviour change. Items retained after applying the matrix-based triangulation process were thematically coded. Ethical approval was granted by the North of Scotland Research Ethics Service., Results: Results from 18 papers, 23 interviewees, 23 participants of focus groups and 61 completed questionnaires in the Delphi survey contributed to the triangulation process. A total of 25 key findings from all four studies were identified during triangulation. There was good convergence; 21 key findings were agreed and remained to inform recommendations. The items were coded as practical/technical (eg, decision about the unique patient identifier to use), mandatory (eg, governed by statute), essential (consistently mentioned in all studies and therefore needed to ensure professional support) or preferable., Conclusions: The development of a paediatric linked database has support from professional stakeholders and HCPs in Scotland. The triangulation identified three sets of core requirements for a new system of data linkage. An additional fourth set of 'preferable' requirements might increase engagement of HCPs and their support for the new system., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Adverse drug events are a major cause of patient safety incidents. Current systems of pharmacovigilance under-report adverse drug reactions (ADRs), especially in children, leading to delays in their identification. This is of particular concern, as children especially have an increased vulnerability to ADRs., Objectives: The objective was to seek consensus among healthcare professionals (HCPs) about barriers and facilitators to the linkage of routinely collected health data for pediatric pharmacovigilance in Scotland., Methods: A Delphi survey was conducted with a random sample of HCPs including nurses, pharmacists and doctors, working in primary or secondary care, in Scotland. Participants were identified from sampling frames of the target professionals such as an NHS workforce list for general practitioners and recruited by postal invitation. A total of 819 HCPs were invited to take part. Those agreeing to participate were given the option of completing the questionnaires online or as hard copy. Reminders were sent twice at a fortnightly interval. Questions content included description of professional role as well as testing for the willingness to support the proposed project and was informed by the Theoretical Domains Framework of Behavior Change (TDF) and earlier qualitative work. Three Delphi rounds were administered, including a first round for item generation., Results: 121 of those invited agreed to take part (15%). The first round of the Delphi study included 21 open questions and generated over a 1000 individual statements from 61 participants that returned the questionnaires (50.4%). These were rationalized to 149 items for the second round in which participants rated their views on the importance (or not) of each item on a 9-point Likert scale (strongly disagree - strongly agree). After the third round, there was consensus on items that focused on professional standards, and practical requirements, overall there was support for data linkage and a multi-professional approach., Conclusions: It would be acceptable to stakeholders to introduce a data linkage system for pharmacovigilance as long as identified concerns are addressed. Concerns included adherence to current professional, legal and ethical standards, as well resolving practical issues., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Most psychiatric inpatients receive psychopharmacological treatment indicated for their mental diseases. The aim of this systematic review is to give clinical pharmacists and physicians a comprehensive summary of common drug-related problems (DRPs) in adult psychiatric inpatients and of potential interventions to solve them in clinical practice. Methods: Six databases and registers were searched for English, German and French articles published between 1999 and 2023 with content regarding the prevalence and/or type or interventions to solve DRPs in adult psychiatric inpatients. Studies were categorized based on types of DRPs and clinical interventions. The prevalence rates of DRPs and subtypes were compared quantitatively and the tested interventions were summarized qualitatively. Results: A total of 88 articles with an overall sample of over 95.425 adult psychiatric inpatients were included in this review. DRPs were reported with a prevalence range of 0.32 to 9.48 per patient. The most frequently reported DRPs were caused by prescribing errors (1.91 per patient), the most frequent subtype was drug interaction (0.77 per patient). Clinical pharmacists were involved in interventions in 7 of 13 included articles. Interventions consisted of clinical pharmacy services on the ward, educational classes, medication reviews, and the implementation of digital tools such as dispensing cabinets and prescribing tools. Discussion: The included studies were heterogeneous. The most frequent DRPs in psychiatry are related to prescribing errors and drug interactions. Clinical pharmacists may support the drug therapy by identifying and effectively solving DRPs in psychiatric inpatients using interdisciplinary approaches. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42022354958. [ABSTRACT FROM AUTHOR]

Reports linking proton pump inhibitors (PPIs) with cognition and dementia show conflicting results, with limited evidence on underlying biological mechanisms. However, existing studies did not investigate brain microstructure, which could provide valuable insights into early structural changes indicative of cognitive decline. Analyses were based on cross-sectional baseline data from the Rhineland Study (n = 7,465; mean age 55.3 ± 13.7 years, range 30–95 years, 56.5% women). Using multivariate linear regression, we investigated associations between PPI use and cognition and brain macro- and microstructural measures (fractional anisotropy (FA) and mean diffusivity (MD) as measures of white matter integrity). Analyses were stratified by short-term (< 3 years) and long-term (≥ 3 years) PPI use, with additional age stratification (< 65 years; ≥65 years) for cognitive outcomes. PPI users, especially younger individuals, showed poorer global cognition and working memory. Notably, younger long-term users had worse total memory. PPI use was not associated with brain volume or FA, but both short-term and long-term users showed higher MD in cognitive-related brain regions. Our findings indicate that prolonged PPI use, particularly in younger long-term users, is associated with poorer cognitive performance. Moreover, PPI users showed higher MD, indicating potential white matter integrity disruptions. Further research is needed to ascertain causality and underlying mechanisms behind PPI-related cognitive decline. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess opinions of frontline healthcare professionals on the linking of routinely collected national (Scottish) paediatric data for the purpose of identifying earlier signals of adverse drug reactions., Methods: Stratified purposive sampling led to profession-specific focus groups with pharmacists, nurses and medical doctors from primary and secondary care in different Scottish Health Boards. A topic guide was used to explore the proposed data linkage of routinely collected paediatric data. Discussions were audio recorded and transcribed verbatim. Transcripts were analysed using a framework approach to identify themes. Ethical approval was obtained from the North of Scotland Research Ethics Service., Results: Six focus groups were conducted in 2011 with 22 participants. Views of the proposed data linkage were generally positive. Several issues were identified, including lack of clarity on data ownership and concerns about diversion of funding. Identified issues were at a practical rather than a strategic level., Conclusions: This study identified that professional stakeholder groups are likely to find linkage of paediatric patient data acceptable. Barriers identified could be addressed. Focus group participants commented on the importance of informing patients and members of the public about the benefits of linking healthcare data. These findings clarify the steps that should be taken to ensure the acceptability of data linkage for pharmacovigilance., (© 2014 The British Pharmacological Society.)

Objective: The inclusion of the Community Health Index in the recording of National Health Service (NHS) contacts in Scotland facilitates national linkage of data such as prescribing and healthcare utilisation. This linkage could be the basis for identification of adverse drug reactions. The aim of this article is to report the views of healthcare professionals on data sharing, ownership and the legal and other applicable frameworks relevant to linkage of routinely collected paediatric healthcare data., Design: Qualitative study using semistructured face-to-face interviews addressing the study aims., Participants: Purposive sample of professional stakeholders (n=25) including experts on ethics, data protection, pharmacovigilance, data linkage, legal issues and prescribing. Interviews were audio-recorded, transcribed and thematically analysed using a framework approach., Results: Participants identified existing data sharing systems in the UK. Access to healthcare data should be approved by the data owners. The definition of data ownership and associated legal responsibilities for linked healthcare data were seen as important factors to ensure accountability for the use of linked data. Yet data owners were seen as facilitators of the proposed data linkage. Twelve frameworks (legal, regulatory and governance) applicable to the linkage of healthcare data were identified., Conclusions: A large number of potentially relevant legal and regulatory frameworks were identified. Ownership of the linked data was seen as an extension of responsibility for, or guardianship of, the source datasets. The consensus emerging from the present study was that clarity is required on the definition of data sharing, data ownership and responsibilities of data owners.

Objective: To review the literature on the views of healthcare professionals to the linkage of healthcare data and to identify any potential barriers and/or facilitators to participation in a data linkage system., Methods: Published papers describing the views of healthcare professionals (HCPs) to data sharing and linkage were identified by searches of Medline, EMBASE, SCOPUS, CINAHL, and PsychINFO. The searches were limited to papers published in the English language from 2001 to 2011., Results: A total of 2917 titles were screened. From these, 18 papers describing the views of HCPs about data linkage or data sharing of routinely collected healthcare data at an individual patient level were included. Views were generally positive, and potential benefits were reported. Facilitators included having trust in the system including data governance, reliability, and feedback. Some negative views, identified as barriers were also expressed including costs, data governance, technical issues, and privacy concerns. Effects on the physician-patient relationship, and workload were also identified as deterrent., Discussion: From the published literature included in this review, the views of HCPs were in general positive towards data sharing for public health purposes. The identification of barriers to contributing to a data linkage system allows these to be addressed in a planned data linkage project for pharmacovigilance. The main barriers identified were concerns about costs, governance and interference with the prescriber-patient relationship. These would have to be addressed if healthcare professionals are to support a data linkage system to improve patient safety.

Background: Postoperative delirium (POD) is the most common complication following surgery in elderly patients. During pharmacist-led medication reconciliation (PhMR), a predictive risk score considering delirium risk-increasing drugs and other available risk factors could help to identify risk patients. Methods: Orthopaedic and trauma surgery patients aged ≥ 18 years with PhMR were included in a retrospective observational single-centre study 03/2022-10/2022. The study cohort was randomly split into a development and a validation cohort (6:4 ratio). POD was assessed through the 4 A's test (4AT), delirium diagnosis, and chart review. Potential risk factors available at PhMR were tested via univariable analysis. Significant variables were added to a multivariable logistic regression model. Based on the regression coefficients, a risk score for POD including delirium risk-increasing drugs (DRD score) was established. Results: POD occurred in 42/328 (12.8%) and 30/218 (13.8%) patients in the development and validation cohorts, respectively. Of the seven evaluated risk factors, four were ultimately tested in a multivariable logistic regression model. The final DRD score included age (66–75 years, 2 points; > 75 years, 3 points), renal impairment (eGFR < 60 ml/min/1.73m2, 1 point), anticholinergic burden (ACB-score ≥ 3, 1 point), and delirium risk-increasing drugs (n ≥ 2; 2 points). Patients with ≥ 4 points were classified as having a high risk for POD. The areas under the receiver operating characteristic curve of the risk score model were 0.89 and 0.81 for the development and the validation cohorts, respectively. Conclusion: The DRD score is a predictive risk score assessable during PhMR and can identify patients at risk for POD. Specific preventive measures concerning drug therapy safety and non-pharmacological actions should be implemented for identified risk patients. [ABSTRACT FROM AUTHOR]

Introduction: In 2021, a computerized physician order entry (CPOE) system with an integrated clinical decision support system (CDSS) was implemented at a tertiary care center for the treatment of mental health conditions in Lübeck, Germany. To date, no study has been reported on the types and prevalence of drug-related problems (DRPs) before and after CPOE implementation in a psychiatric inpatient setting. The aim of this retrospective before-and-after cohort study was to investigate whether the implementation of a CPOE system with CDSS accompanied by the introduction of regular medication plausibility checks by a pharmacist led to a decrease of DRPs during hospitalization and unsolved DRPs at discharge in psychiatric inpatients. Methods: Medication charts and electronic patient records of 54 patients before (cohort I) and 65 patients after (cohort II) CPOE implementation were reviewed retrospectively by a clinical pharmacist. All identified DRPs were collected and classified based on 'The PCNE Classification V9.1', the German database DokuPIK, and the 'NCC MERP Taxonomy of Medication Errors'. Results: 325 DRPs were identified in 54 patients with a mean of 6 DRPs per patient and 151.9 DRPs per 1000 patient days in cohort I. In cohort II, 214 DRPs were identified in 65 patients with a mean of 3.3 DRPs per patient and 81.3 DRPs per 1000 patient days. The odds of having a DRP were significantly lower in cohort II (OR=0.545, 95% CI 0.412-0.721, p<0.001). The most frequent DRP in cohort I was an erroneous prescription (n=113, 34.8%), which was significantly reduced in cohort II (n=12, 5.6%, p<0.001). During the retrospective in-depth review, more DRPs were identified than during the daily plausibility analyses. At hospital discharge, patients had significantly less unsolved DRPs in cohort II than in cohort I. Discussion: The implementation of a CPOE system with an integrated CDSS reduced the overall prevalence of DRPs, especially of prescription errors, and led to a smaller rate of unsolved DRPs in psychiatric inpatients at hospital discharge. Not all DRPs were found by plausibility analyses based on the medication charts. A more interactive and interdisciplinary patient-oriented approach might result in the resolution of more DRPs. [ABSTRACT FROM AUTHOR]

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There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood–brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects. [ABSTRACT FROM AUTHOR]

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Objective is to measure the rate and prevalence of PIM dispensing and to identify problematic practices in Switzerland.Material and Methods: The studied population includes about 90,000 insured over 17 years old from a Swiss health maintenance organization in 2019 and 2020. We computed and compared the number of PIM per patient for Beers criteria, Priscus list, Laroche, NORGEP and Prescrire approaches. We also created a composite indicator that accounts for the specificities of the Swiss context (adaptation to the Swiss drugs' market, recommendations in force related to sleeping pills, anxiolytics and NSAIDs). We also stratified the analysis per physician, including initiation and cessation of PIM prescription.Results: Our comparison revealed similarities between the approaches, but also that each of them had specific gaps that provides further motivation for the development of a composite approach. PIM rate was particularly high for sleeping pills, anxiolytics, NSAIDs, even when analyses were limited to chronic use. Drugs with anticholinergic effect were also frequently prescribed. Based on our composite indicator, 27% of insured over 64 years old received at least one PIM in 2020, and 8% received more than one. Our analyses also reveal that for sleeping pills and anxiolytics, half of the volume (or prevalence?) occurs in the < 65 population. We observed strong variations between physicians and a significant proportion of new users among patients with PIM.Conclusion: Our results show that PIMs prescribing is very frequent in Switzerland and is driven mostly by a few drug categories. There is important physician variation in PIM prescribing that warrants the development of intervention targeted at high PIM-prescribers. [ABSTRACT FROM AUTHOR]

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We aimed to evaluate the association between polypharmacy, anticholinergic burden, comorbidities, and hospital length of stay in older adults. We analyzed 213 older in-patient data retrospectively. Demographic data, comorbidities, length of stay, medication use, and laboratory results at admission were extracted from electronic medical records. We used a calculator to work out Anticholinergic Burden (ACB). The use of five or more drugs was considered polypharmacy. The mean age was 78±7.3 years; 54.5% of patients were female. The mean length of stay of patients was 20.7±13.8 days. The prevalence of polypharmacy was 66.2% (n:141), and 182 (85.4%) of the patients were treated with anticholinergic medications. 52.6% had high ACB scores (ACB score 3 and more). The most used drugs with anticholinergic potential were metoprolol (40.4%) and metformin (32.4%). Polypharmacy was identified as a risk factor for the presence of high ACB with 86% sensitivity and 55% specificity. (OR 0.758 95% CI: 0.692-0.824, p: <0.001). High ACB score was an independent risk factor for the presence of length of stay (OR: 1.19, 95% CI: 1.10-1.29, p: <0.001), diabetes mellitus (OR: 3.15, 95% CI: 1.08-9.18, p=0.035), coronary artery disease (OR: 5.32, 95% CI: 1.65-17.11, p=0.005), atrial fibrillation (OR: 4.94, 95% CI: 1.30-18.83, p=0.019), depression (OR: 10.96, 95% CI: 3.28-36.58, p: <0.001), psychotic disorder (OR: 80.53, 95% CI: 4.72-1372.05, p=0.002), Parkinson's disease (OR: 3.65, 95% CI: 1.21-11.01, p=0.021), and rheumatological illness (OR: 5.89, 95% CI: 1.20-28.97, p=0.029). Polypharmacy, length of stay, and comorbidities such as cardiometabolic diseases (diabetes mellitus, coronary artery disease, atrial fibrillation), psychiatric and neurological disorders (depression, psychotic disorder, Parkinson's), and rheumatological illness are significantly associated with ACB. It is crucial to be aware of the ACB for rational drug use and optimum treatment of comorbidities to prevent adverse outcomes in older patients. [ABSTRACT FROM AUTHOR]

Background: Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research. Methods: A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0–3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process. Results: The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group. Conclusions: Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes. [ABSTRACT FROM AUTHOR]

Postural instability and freezing of gait are the most debilitating dopamine-refractory motor impairments in advanced stages of Parkinson's disease because of increased risk of falls and poorer quality of life. Recent findings suggest an inability to efficaciously utilize vestibular information during static posturography among people with Parkinson's disease who exhibit freezing of gait, with associated changes in cholinergic system integrity as assessed by vesicular acetylcholine transporter PET. There is a lack of adequate understanding of how postural control varies as a function of available sensory information in patients with Parkinson's disease with freezing of gait. The goal of this cross-sectional study was to examine cerebral cholinergic system changes that associate with inter-sensory postural control processing features as assessed by dynamic computerized posturography and acetylcholinesterase PET. Seventy-five participants with Parkinson's disease, 16 of whom exhibited freezing of gait, underwent computerized posturography on the NeuroCom© Equitest sensory organization test platform, striatal dopamine, and acetylcholinesterase PET scanning. Findings demonstrated that patients with Parkinson's disease with freezing of gait have greater difficulty maintaining balance in the absence of reliable proprioceptive cues as compared to those without freezing of gait [ β = 0.28 (0.021, 0.54), P = 0.034], an effect that was independent of disease severity [ β = 0.16 (0.062, 0.26), P < 0.01] and age [ β = 0.092 (−0.005, 0.19), P = 0.062]. Exploratory voxel-based analysis revealed an association between postural control and right hemispheric cholinergic network related to visual-vestibular integration and self-motion perception. High anti-cholinergic burden predicted postural control impairment in a manner dependent on right hemispheric cortical cholinergic integrity [ β = 0.34 (0.065, 0.61), P < 0.01]. Our findings advance the perspective that cortical cholinergic system might play a role in supporting postural control after nigro-striatal dopaminergic losses in Parkinson's disease. Failure of cortex-dependent visual-vestibular integration may impair detection of postural instability in absence of reliable proprioceptive cues. Better understanding of how the cholinergic system plays a role in this process may augur novel treatments and therapeutic interventions to ameliorate debilitating symptoms in patients with advanced Parkinson's disease. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to estimate the association between anticholinergic burden, general cognitive ability and various measures of brain structural MRI in relatively healthy middle‐aged and older individuals. Methods: In the UK Biobank participants with linked health‐care records (n = 163,043, aged 40–71 at baseline), of whom about 17 000 had MRI data available, we calculated the total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general cognitive ability, 9 separate cognitive domains, brain atrophy, volumes of 68 cortical and 14 subcortical areas and fractional anisotropy and median diffusivity of 25 white‐matter tracts. Results: Anticholinergic burden was modestly associated with poorer cognition across most anticholinergic scales and cognitive tests (7/9 FDR‐adjusted significant associations, standardised betas (β) range: −0.039, −0.003). When using the anticholinergic scale exhibiting the strongest association with cognitive functions, anticholinergic burden due to only some classes of drugs exhibited negative associations with cognitive function, with β‐lactam antibiotics (β = −0.035, PFDR < 0.001) and opioids (β = −0.026, PFDR < 0.001) exhibiting the strongest effects. Anticholinergic burden was not associated with any measure of brain macrostructure or microstructure (PFDR > 0.08). Conclusions: Anticholinergic burden is weakly associated with poorer cognition, but there is little evidence for associations with brain structure. Future studies might focus more broadly on polypharmacy or more narrowly on distinct drug classes, instead of using purported anticholinergic action to study the effects of drugs on cognitive ability. [ABSTRACT FROM AUTHOR]

Background: Pharmaceutical decision support systems (PDSSs) use reasoning software to match patient data to modelled situations likely to cause drug-related problems (DRPs) or adverse drug events. To aid decision-making, modelled situations must be linked to well-defined systemic clinical risks., Aim: To obtain expert consensus on the level of clinical risk for patients associated with each modelled situation that could be addressed using a PDSS., Method: A two-round e-Delphi survey was conducted from February to April 2022, involving 20 experts from four French-speaking countries. Participants had to rate modelled situations on two five-point Likert scales, assessing the likelihood of clinical consequences and their severity. The degree of consensus was determined as the proportion of participants providing risk scores in line with the median. The combined median scores for likelihood and severity provided the level of risk according to the Clinical Risk Situation for Patients (CRiSP) scale, formalized via validated tools., Results: The expert panel achieved consensus (≥ 75% agreement) on 48 out of 52 modelled clinical situations. Among these, 45 were categorized as high or extreme risk. The most common DRP identified was overdosing, accounting for 22% of cases. Furthermore, DRPs involving cardiovascular, psychiatric, and endocrinological drug classes were prevalent, constituting 45, 13, and 9% of cases, respectively., Conclusion: Through consensus, our study identified 45 modelled clinical situations associated with high or extreme risks. This study highlights the interest of using PDSSs to prevent harm in patients and, on a large scale, document the impact of the pharmacist in preventing, intercepting and managing iatrogenic drug risk., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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Anticholinerge bijwerkingen van geneesmiddelen kunnen met name voor ouderen schadelijk zijn. Er wordt daarom aangeraden het gebruik van geneesmiddelen met anticholinerge bijwerkingen bij ouderen te beperken. In verscheidene richtlijnen wordt aangeraden om amitriptyline bij ouderen te vervangen door nortriptyline, omdat de anticholinerge werking van nortriptyline minder sterk zou zijn. In hoeverre wordt deze keuze door wetenschappelijk onderzoek onderbouwd? Geeft nortriptyline inderdaad minder anticholinerge bijwerkingen dan amitriptyline en is het verschil in het anticholinerge effect te kwantificeren? [ABSTRACT FROM AUTHOR]

Background: Older people living in residential aged care facilities are at high risk of acquiring infections such as influenza, gastroenteritis, and more recently COVID-19. These infections are a major cause of morbidity and mortality among this cohort. Quality infection prevention and control practice in residential aged care is therefore imperative. Although appointment of a dedicated infection prevention and control (IPC) lead in every Australian residential aged care facility is now mandated, all people working in this setting have a role to play in IPC. The COVID-19 pandemic revealed inadequacies in IPC in this sector and highlighted the need for interventions to improve implementation of best practice. Methods: Using mixed methods, this four-phase implementation study will use theory-informed approaches to: (1) assess residential aged care facilities' readiness for IPC practice change, (2) explore current practice using scenario-based assessments, (3) investigate barriers to best practice IPC, and (4) determine and evaluate feasible and locally tailored solutions to overcome the identified barriers. IPC leads will be upskilled and supported to operationalise the selected solutions. Staff working in residential aged care facilities, residents and their families will be recruited for participation in surveys and semi-structured interviews. Data will be analysed and triangulated at each phase, with findings informing the subsequent phases. Stakeholder groups at each facility and the IMMERSE project's Reference Group will contribute to the interpretation of findings at each phase of the project. Discussion: This multi-site study will comprehensively explore infection prevention and control practices in residential aged care. It will inform and support locally appropriate evidence-based strategies for enhancing infection prevention and control practice. [ABSTRACT FROM AUTHOR]

Background: Anticholinergic burden has been associated with adverse outcomes such as falls. To date, no gold standard measure has been identified to assess anticholinergic burden, and no conclusion has been drawn on which of the different measure algorithms best predicts falls in older patients from general practice. This study compared the ability of five measures of anticholinergic burden to predict falls. To account for patients' individual susceptibility to medications, the added predictive value of typical anticholinergic symptoms was further quantified in this context. Methods and findings: To predict falls, models were developed and validated based on logistic regression models created using data from two German cluster-randomized controlled trials. The outcome was defined as "≥ 1 fall" vs. "no fall" within a 6-month follow-up period. Data from the RIME study (n = 1,197) were used in model development, and from PRIMUM (n = 502) for external validation. The models were developed step-wise in order to quantify the predictive ability of anticholinergic burden measures, and anticholinergic symptoms. In the development set, 1,015 patients had complete data and 188 (18.5%) experienced ≥ 1 fall within the 6-month follow-up period. The overall predictive value of the five anticholinergic measures was limited, with neither the employed anticholinergic variable (binary / count / burden), nor dose-dependent or dose-independent measures differing significantly in their ability to predict falls. The highest c-statistic was obtained using the German Anticholinergic Burden Score (0.73), whereby the optimism-corrected c-statistic was 0.71 after interval validation using bootstrapping and 0.63 in the external validation. Previous falls and dizziness / vertigo had the strongest prognostic value in all models. Conclusions: The ability of anticholinergic burden measures to predict falls does not appear to differ significantly, and the added value they contribute to risk classification in fall-prediction models is limited. Previous falls and dizziness / vertigo contributed most to model performance. [ABSTRACT FROM AUTHOR]

Background: The term potentially inadequate medication (PIM) is used to describe substances that may be unsuitable for use in the elderly and should be avoided. The PRISCUS list, published in 2010, was the first catalog of PIM designed for the German drug market to become adopted in practice. While 24% of German patients aged ≥ 65 years were prescribed at least one PIM per year in 2009, the proportion in 2019 was only 14.5%. Methods: In a three-round Delphi process, experts from clinical practice and research evaluated whether selected substances are PIM for the elderly. The participants were provided with dedicated literature including systematic reviews carried out for the particular purposes of this project. Results: Fifty-nine persons took part in the Delphi process and, in addition, contributed comments and therapeutic alternatives. Altogether, 187 substances were classed as PIM. One hundred thirty-three of the substances now listed were not in the original PRISCUS list: these include some oral antidiabetics, all of the selective COX-2 inhibitors, and moderately long acting benzodiazepines such as oxazepam. For some other substances, e.g., proton pump inhibitors (PPI), the advisability of treatment for more than 8 weeks was considered as potentially inappropriate, as was the use of ibuprofen in doses >1200 mg/day and for more than 1 week without PPI. Risperidone for more than 6 weeks is also PIM. Conclusion: The new, greatly extended PRISCUS list must now be validated in epidemiological and prospective studies and its practicability in routine daily use must be verified. [ABSTRACT FROM AUTHOR]

Objectives: To identify the barriers and facilitators that people with severe mental illness and people with learning disabilities may encounter when accessing cancer screening and make recommendations for implementing reasonable adjustments throughout cancer screening services. Methods and analysis: An 18-month sequential, mixed-methods study comprising of two phases of work and underpinned by Normalisation Process Theory, recruiting from across the North-East and North Cumbria. The first phase aims to identify the barriers and facilitators for people with severe mental illness in accessing cervical, breast and colorectal cancer screening. A systematic review of eight databases (Part 1a; PROSPERO registration number: CRD42022331781) alongside semi-structured interviews of up to 36 people with severe mental illness (Part 1b) will occur. Additional characteristics indicating populations whose perspectives may not have been accounted for in the systematic review will be targeted in the interviews. Potential participants will be identified from a range of settings across the North-East and North Cumbria, including through social media and gatekeepers within National Health Service Trusts and charities. Interviews will be analysed using framework analysis, which will be in line with the Normalisation Process Theory. The second phase of the project (part 2a) involves triangulating the results of the systematic review and interviews with existing research previously completed with people with learning disabilities accessing cancer screening. This will be to identify population specific barriers and facilitators across people with learning disabilities and people with severe mental illness to access cancer screening services. Following triangulation, part 2b will include designing and planning a future study involving stakeholders in cancer screening to explore the feasibility, practicality, and priority for implementing the recommendations to improve person centred cancer screening services (PECCS). Ethics and dissemination: This study has received Teesside University ethical approval, Health Research Authority approval (IRAS: 310622) and favourable opinion (REF: 22/PR/0793). Findings will be disseminated through a range of academic and non-academic modes including infographics, blog posts and academic publications. [ABSTRACT FROM AUTHOR]

Aims: A recent review identified 19 anticholinergic burden scales (ABSs) but no study has yet compared the impact of all 19 ABSs on delirium. We evaluated whether a high anticholinergic burden as classified by each ABS is associated with incident delirium. Method: We performed a retrospective cohort study in a Swiss tertiary teaching hospital using data from 2015–2018. Included were patients aged ≥65, hospitalised ≥48 hours with no stay >24 hours in intensive care. Delirium was defined twofold: (i) ICD‐10 or CAM and (ii) ICD‐10 or CAM or DOSS. Patients' cumulative anticholinergic burden score, calculated within 24 hours after admission, was classified using a binary (<3: low, ≥3: high burden) and a categorical approach (0: no, 0.5–3: low, ≥3: high burden). Association was analysed using multivariable logistic regression. Results: Over 25 000 patients (mean age 77.9 ± 7.6 years) were included. Of these, (i) 864 (3.3%) and (ii) 2770 (11.0%) developed delirium. Depending on the evaluated ABS, 4–63% of the patients were exposed to at least one anticholinergic drug. Out of 19 ABSs, (i) 14 and (ii) 16 showed a significant association with the outcomes. A patient with a high anticholinergic burden score had odds ratios (ORs) of 1.21 (95% confidence interval [CI]: 1.03–1.42) to 2.63 (95% CI: 2.28–3.03) for incident delirium compared to those with low or no burden. Conclusion: A high anticholinergic burden within 24 hours after admission was significantly associated with incident delirium. Although prospective studies need to confirm these results, discontinuing or substituting drugs with a score of ≥3 at admission might be a targeted intervention to reduce incident delirium. [ABSTRACT FROM AUTHOR]

Purpose: In older adults, fractures are associated with mortality, disability, loss of independence and high costs. Knowledge on their predictors can help to identify persons at high risk who may benefit from measures to prevent fractures. We aimed to assess the potential of German claims data to predict fractures in older adults. Patients and Methods: Using the German Pharmacoepidemiological Research Database (short GePaRD; claims data from ~20% of the German population), we included persons aged ≥ 65 years with at least one year of continuous insurance coverage and no fractures prior to January 1, 2017 (baseline). We randomly divided the study population into a training (80%) and a test sample (20%) and used logistic regression and random forest models to predict the risk of fractures within one year after baseline based on different combinations of potential predictors. Results: Among 2,997,872 persons (56% female), the incidence per 10,000 person years of any fracture in women increased from 133 in age group 65– 74 years (men: 71) to 583 in age group 85+ (men: 332). The maximum predictive performance as measured by the area under the curve (AUC) across models was 0.63 in men and 0.60 in women and was achieved by combining information on drugs and morbidities. AUCs were lowest in age group 85+. Conclusion: Our study showed that the performance of models using German claims data to predict the risk of fractures in older adults is moderate. Given that the models used data readily available to health insurance providers in Germany, it may still be worthwhile to explore the cost–benefit ratio of interventions aiming to reduce the risk of fractures based on such prediction models in certain risk groups. [ABSTRACT FROM AUTHOR]

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Our study was carried out as part of updating the I Potentially inappropriate medications list in the elderly i in Germany (henceforth termed "the PRISCUS list").[1] This included a three-round Delphi process to derive the list of PIMs. Our aim was to investigate the process of providing information and the importance of different sources of information in the context of developing a PIM list. Altogether, 187 substances were classed as PIM.[4] We conducted a closed follow-up survey of all experts who took part in the assessment of PIM for the update of the PRISCUS list. [Extracted from the article]

The number of patients with dementia is expected to grow in the coming years due to an aging population and an increasing life-expectancy. At the same time, in an aging society there will be an increase in multimorbidity and therefore polypharmacy. This combination presents numerous challenges particularly for people with dementia, as the correct administration of the drugs can frequently no longer be guaranteed. The drug treatment of neuropsychiatric symptoms of dementia are often treated with antipsychotics with potentially severe side effects and with limited efficacy. Moreover, many drugs have an anticholinergic potential, which may worsen the cognitive function even further in patients with dementia. The use of anticholinergic drugs should be handled with care and when possible be avoided in patients with dementia., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: In a large proportion of patients admitted to the emergency department (ED), the initial main symptom is nonspecific. One possible reason for this, especially in older patients, may be adverse drug reactions (ADR) due to their frequent polypharmacy., Aim: To illustrate the incidence of ADRs, the affected patient population including risk factors, and drug classes with ADRs leading to nonspecific symptoms. To provide practice recommendations for the management of ADRs in the ED., Material and Methods: Presentation of the pharmacological principles on ADRs, statistics of pharmacovigilance centers as well as original literature including experiences from clinical practice and own projects., Results: In 10% of patients with nonspecific symptoms an ADR is responsible for presentation in the ED. In 60% of cases these ADRs are not correctly identified in the ED setting. A small number of drug classes are responsible for most of these referrals. Databases, risk stratification, clinical pharmacists, or clinical decision support systems are available to improve ADR identification and management. As these options are partly associated with considerable costs or the validation for German EDs is missing, a widespread application does not take place., Conclusion: Correct identification of ADRs in patients with nonspecific symptoms in the ED is necessary to initiate adequate treatment. These ADRs are often overlooked because processes and tools for identification and management are not applied in the ED, leading to a lack of awareness. For high-risk patients in the ED, the focus should be on drug history, ideally considering patient-specific risk factors and specific drug classes., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Older people often suffer from multimorbidity resulting in polypharmacy. The correct administration of medication is a crucial factor influencing treatment efficacy. However, tools for evaluating the ability to self-administer different dosage forms of medications are lacking. The objectives of the ABLYMED study are to 1) assess the ability to self-administer different dosage forms of medication in older non-demented in-hospital patients who report autonomous management of medication, 2) identify factors influencing the ability to self-administer medication, and 3) develop a standardized tool to validly assess the ability to self-administer different dosage forms of medications based on the final study results.Methods: One hundred in-patients from the department of orthopedics and trauma surgery of the University Hospital Düsseldorf  ≥ 70 years of age and regularly taking ≥ 5 different drugs autonomously will be prospectively recruited into the observational cross-sectional single-center ABLYMED study. Patients undergo an interview addressing demographic and clinical information, medication history (which medications are taken since when, in which dose and dosage form, and subjective proficiency of taking these medications), medication adherence, and factors possibly influencing adherence including personality traits and perceived quality of the medication regimen. Quality of the medication regimen is also rated by clinicians according to validated lists. Further, patients receive a comprehensive geriatric assessment including measures of cognition, mobility, and functional status. The ability to self-administer medication is assessed by having patients perform different tasks related to medication self-administration, which are video recorded and rated by different experts. The patients' self-reported ability will be correlated with the observed performance in the self-administration tasks. Further, factors correlating with the reported and observed ability to self-administer medication will be evaluated using correlation and regression models. Based on the final study results, a novel tool to assess the ability of older patients to self-administer medication will be developed.Discussion: In addition to guideline-based pharmacotherapy, correct intake of prescribed medication is crucial for optimal therapy of multimorbidity in older people. Tools to validly assess the ability of older patients to self-administer different dosage forms of medications are lacking, but should be included in comprehensive geriatric assessments to secure functional health.Trial Registration: Development of an assessment instrument to evaluate the ability to manage various dosage forms, DRKS-ID: DRKS00025788 , (date of registration: 07/09/2021). [ABSTRACT FROM AUTHOR]

Background: The use of prescription drugs with anticholinergic properties has been associated with multiple negative health outcomes in older people. Moreover, recent evidence suggests that associated adverse effects may occur even decades after stopping anticholinergic use. Despite the implicated importance of examining longitudinal patterns of anticholinergic prescribing for different age groups, few such data are available. Methods: We performed an age‐period‐cohort (APC) analysis to study trends in an aggregate measure of anticholinergic burden between the years 1990 and 2015, utilising data from >220 000 UK Biobank participants with linked prescription data from primary care. Results: Anticholinergic burden in the sample increased up to 9‐fold over 25 years and was observed for both period and age effects across most classes of drugs. The greatest increase was seen in the prescribing of antidepressants. Female sex, lower education and greater deprivation were associated with greater anticholinergic burden. Conclusions: The increase in anticholinergic prescribing is mostly due to an increase in polypharmacy and is attributable to both ageing of participants and period‐related changes in prescribing practices. Research is needed to clarify the implications of rising anticholinergic use for public health and to contextualise this rise in light of other relevant prescribing practices. [ABSTRACT FROM AUTHOR]

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Background: Anticholinergic (ACH) medications have been associated with neurocognitive impairment, particularly in the elderly. This study determined prospectively the prevalence of prescribed ACH medications and their association with self-reported neurocognitive impairment (SRNI) in elderly people living with HIV (PLWH) of the Swiss HIV Cohort Study (SHCS).Methods: A literature review was performed to identify ACH medications, which were scored 0 to 3 (higher score indicating more ACH burden). Prescriptions were reviewed in July 2019 for all SHCS participants ≥65 years old to assess the prevalence of ACH medications. Association between ACH burden and neurocognitive impairment was evaluated using the SHCS SRNI questions addressing memory loss, attention difficulties and slowing in reasoning.Results: One thousand and nineteen PLWH (82% male) with a median age of 70 (IQR = 67-74) years were included. Most participants were on ART (99%). The average number of non-HIV drugs was 5.1 ± 3.6, representing a polypharmacy prevalence of 50%. Two hundred participants (20%) were on ≥1 ACH medication, with an average ACH score of 1.7 ± 1.3. SRNI, adjusted for age, sex, CD4, nadir CD4, viral load, efavirenz use and polypharmacy, was associated with depression (OR = 4.60; 95% CI = 2.62-8.09) and a trend was observed with being on ≥1 ACH medication (OR = 1.69; 95% CI = 0.97-2.95). In a subgroup analysis of participants without depression (n = 911), SRNI was associated with the use of ≥1 ACH medication (OR = 2.51; 95% CI = 1.31-4.80).Conclusions: ACH medication use is common in elderly PLWH and contributes to SRNI. The effect of ACH medications on neurocognitive impairment warrants further evaluation using neurocognitive tests. [ABSTRACT FROM AUTHOR]

Although no gold standard exists to assess a patient's anticholinergic burden, a review identified 19 anticholinergic burden scales (ABSs). No study has yet evaluated whether a high anticholinergic burden measured with all 19 ABSs is associated with in‐hospital mortality and length of stay (LOS). We conducted a cohort study at a Swiss tertiary teaching hospital using patients' electronic health record data from 2015–2018. Included were patients aged ≥65 years, hospitalised ≥48 h without stays and >24 h in intensive care. Patients' cumulative anticholinergic burden score was classified using a binary (<3: low, ≥3: high) and categorical approach (0: no, 0.5–3: low, ≥3: high). In‐hospital mortality and LOS were analysed using multivariable logistic and linear regression, respectively. We included 27,092 patients (mean age 78.0 ± 7.5 years, median LOS 6 days). Of them, 913 died. Depending on the evaluated ABS, 1370 to 17,035 patients were exposed to anticholinergics. Patients with a high burden measured by all 19 ABSs were associated with a 1.32‐ to 3.03‐fold increase in in‐hospital mortality compared with those with no/low burden. We obtained similar results for LOS. To conclude, discontinuing drugs with anticholinergic properties (score ≥3) at admission might be a targeted intervention to decrease in‐hospital mortality and LOS. [ABSTRACT FROM AUTHOR]

Background: Previous studies on the relationship between anticholinergic drugs and dementia have reported heterogeneous results. This variability could be due to different anticholinergic scales and differential effects of distinct classes of drugs. Methods: Using Cox proportional hazards models, we computed the association between annual anticholinergic burden (AChB) and the risk of dementia inUK Biobank with linked general practitioner prescription records between the years 2000 and 2015 (n = 171,775). Results:AChB according to most anticholinergic scales (standardized odds ratio range: 1.027-1.125) and the slope of the AChB trajectory (hazard ratio = 1.094; 95% confidence interval: 1.068-1.119) were predictive of dementia. However, the association between AChB and dementia held only for some classes of drugs, especially antidepressants, antiepileptics, and antidiuretics. Discussion: The heterogeneity in previous findings may partially be due to different effects for different classes of drugs. Future studies should establish differences in more detail and further examine the practicality of a general measure of AChB relating to the risk of dementia. [ABSTRACT FROM AUTHOR]