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ObjectiveTo synthesise the current knowledge on barriers and facilitators to deprescribing cardiovascular medications (CVMs) at the levels of patients, informal caregivers and healthcare providers (HCPs).Design/settingWe conducted a systematic review of studies exploring/assessing patient, informal caregiver and/or HCP barriers and/or facilitators to deprescribing CVMs.Data sourcesOvid/MEDLINE and Embase from January 2003 to November 2021.Data extraction and synthesisWe performed a deductive thematic analysis based on the framework of specific barriers and facilitators to deprescribing CVMs created by Goyal et al. We added a quantification of the occurrence of categories and themes in the selected articles to identify the resounding themes that indicate the greater impetus to address in future research.ResultsMost frequent deprescribing barriers for patients, informal caregivers and HCPs included uncertainty due to lack of evidence regarding CVM deprescribing (in n=10 studies), fear of negative consequences following deprescribing (n=13) and social influences (n=14). A frequently reported facilitator to deprescribing, especially for patients and informal caregivers, was the occurrence of adverse drug events (n=7). Another frequently reported facilitator for patients were dislike of CVMs (n=9). Necessity and benefit of CVMs were seen as barriers or facilitators similarly by patients and HCPs.ConclusionThe differences in patient, informal caregiver and HCP regarding barriers and facilitators to deprescribing CVMs stress the need for ground discussions about beliefs and preferences of each stakeholder implicated in deprescribing decisions. Furthermore, HCP uncertainty regarding CVM deprescribing highlights the need to provide HCPs with tools that enable sharing the risks and benefits of deprescribing with patients and ensure a safe deprescribing process.PROSPERO registration numberCRD42020221973.

Background: There is little evidence for statins for primary cardiovascular prevention in older adults. Consequently, it is important to assess patient attitudes toward the use of statins, which might differ from attitudes toward other medications. We aimed to describe older patient attitudes toward deprescribing statins versus general medications. Methods: We conducted a survey using the revised Patients’ Attitudes Toward Deprescribing questionnaire in its original version and adapted to statin use in adults ≥65 years taking a statin for primary prevention. Results: Among the 47 participants (mean age 74.6 years), 42 (89%) were satisfied with their current therapy, but still willing to stop ≥1 of their medications upon their doctor’s advice. About 68% (N = 32) were satisfied with their statin therapy, while 83% (N = 39) would accept to consider deprescribing. Twenty-six (55%) participants were concerned about missing future benefits when stopping their general medications and 17 (36%) when stopping their statin. Eight (17%) participants believed they were experiencing side effects of statins and twice as many for general medication (38%, N = 18). Conclusion: Our study provides insight about differences and similarities in patient attitudes toward deprescribing general medications and statins in primary prevention. This information could support patient-centered conversations and shared-decision making about deprescribing.

Background Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. Results At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p < 0.001), triglycerides (0.11, 0.03–0.20, p = 0.007), log(RANKL) (0.07, 0.02–0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p = 0.001), statin use (0.39, 0.06–0.72, p = 0.023) and duration of follow up (0.04, 0.01–0.06, p = 0.004). Conclusion In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234

ObjectivesIn the context of limited evidence on statin use in primary cardiovascular prevention in older adults, we assessed physician perspectives on decision-making about statin continuation or discontinuation in this population.DesignQualitative descriptive approach including four focus groups. Inductive and deductive thematic analysis.Setting and participants18 physicians including two neurologists, three cardiologists, seven hospital internists and six primary care providers (PCPs) recruited at a hospital and primary care practices in the area of Bern in Switzerland.ResultsConcerning knowledge about statins in older adults, physicians reported defining if a patient is treated for primary or secondary prevention as challenging and that lack of evidence makes the decision to continue or discontinue the statin difficult. In terms of beliefs, fear of a possible rebound effect after statin discontinuation was reported. Regarding decision-making, physicians mentioned that statin discontinuation or continuation should be a shared decision between the patient and the physician. Concerning the professional role, environmental context and resources, the PCP office was identified as the ideal setting to discuss discontinuation, as all necessary information is available and PCPs have a longer relationship with the patients, thus facilitating a shared decision. Discontinuation of a chronic medication was perceived as difficult in general. Furthermore, PCPs noticed a possible negative impact on patient–physician relationship as some patients felt not being worth it, given up or undertreated if the statin was discontinued.ConclusionsThis study highlights the challenges of statin continuation and discontinuation in older patients and the crucial role of PCPs in situations with unclear evidence for a medication, where shared decision-making between physicians and patients is important. More evidence forming the background for a decision aid would be helpful.

Background Despite a lack of evidence, measurement and supplementation of vitamin D remain frequent in the general population, leading to significant and potentially avoidable healthcare costs. The aim of this study was to evaluate the impact of two quality improvement interventions (minimal vs. intensive) on inappropriate vitamin D measurement and supplementation in hospitalized patients and compare the two interventions. Methods We conducted a pre-post intervention study on general internal medicine wards in Switzerland between 01 July 2016 and 31 December 2023. We compared a minimal intervention consisting of short guidelines in one hospital with a more intensive intervention including an e-learning, reminder e-mails and quizzes in a second hospital. Inappropriate measurement and supplementation of vitamin D were defined as measurement/supplementation in the absence of specific conditions associated with vitamin D deficiency (i.e., osteoporosis, osteomalacia, hepatic failure, malabsorption syndrome, chronic kidney disease with hyperparathyroidism, granuloma-forming disorders, or medications affecting vitamin D or bone metabolism). We used difference-in-differences with random-effects regression with bootstrap standard errors to estimate the overall intervention effect on inappropriate vitamin D measurement and supplementation across hospitals and compared the differences between hospitals. Results Among 31,755 hospitalizations, the average monthly percentage of inappropriate vitamin D measurement and supplementation were 4.0% and 20.5%, respectively, over the entire study period. Compared to the pre-intervention period, there was a 1.3% reduction in inappropriate vitamin D measurements after the start of the interventions ( p  = 0.003), with no significant difference between interventions ( p  = 0.98). However, the rate of inappropriate vitamin D supplementation did not significantly change after intervention start ( p  = 0.81). Conclusion Training interventions for residents were associated with a reduction in inappropriate vitamin D measurement, but not supplementation. The lack of significant difference between both interventions, even if not confirming equivalence, suggests that simpler, more passive strategies may be just as effective as more intensive approaches, offering a cost-efficient way to curb low-value care.

The CERN-MEDICIS (MEDical Isotopes Collected from ISolde) facility has delivered its first radioactive ion beam at CERN (Switzerland) in December 2017 to support the research and development in nuclear medicine using non-conventional radionuclides. Since then, fourteen institutes, including CERN, have joined the collaboration to drive the scientific program of this unique installation and evaluate the needs of the community to improve the research in imaging, diagnostics, radiation therapy and personalized medicine. The facility has been built as an extension of the ISOLDE (Isotope Separator On Line DEvice) facility at CERN. Handling of open radioisotope sources is made possible thanks to its Radiological Controlled Area and laboratory. Targets are being irradiated by the 1.4 GeV proton beam delivered by the CERN Proton Synchrotron Booster (PSB) on a station placed between the High Resolution Separator (HRS) ISOLDE target station and its beam dump. Irradiated target materials are also received from external institutes to undergo mass separation at CERN-MEDICIS. All targets are handled via a remote handling system and exploited on a dedicated isotope separator beamline. To allow for the release and collection of a specific radionuclide of medical interest, each target is heated to temperatures of up to 2,300°C. The created ions are extracted and accelerated to an energy up to 60 kV, and the beam steered through an off-line sector field magnet mass separator. This is followed by the extraction of the radionuclide of interest through mass separation and its subsequent implantation into a collection foil. In addition, the MELISSA (MEDICIS Laser Ion Source Setup At CERN) laser laboratory, in service since April 2019, helps to increase the separation efficiency and the selectivity. After collection, the implanted radionuclides are dispatched to the biomedical research centers, participating in the CERN-MEDICIS collaboration, for Research & Development in imaging or treatment. Since its commissioning, the CERN-MEDICIS facility has provided its partner institutes with non-conventional medical radionuclides such as Tb-149, Tb-152, Tb-155, Sm-153, Tm-165, Tm-167, Er-169, Yb-175, and Ac-225 with a high specific activity. This article provides a review of the achievements and milestones of CERN-MEDICIS since it has produced its first radioactive isotope in December 2017, with a special focus on its most recent operation in 2020.

Background In hospital practice, atypical antipsychotics are often used to manage delirium, sleep problems, agitation, or behavioural and psychological symptoms of dementia, while evidence remains uncertain regarding effectiveness and safety for those off-label indications. While guidelines to reduce inappropriate prescribing have been published, prescribing patterns in older multimorbid patients are not well understood. We thus aimed to investigate the patterns of prescribing and deprescribing of atypical antipsychotics over one year following an acute hospitalisation, as well as the appropriateness of prescriptions. Methods We conducted a longitudinal analysis using data from the OPERAM trial, a European multicentre study assessing hospital pharmacotherapy optimisation in multimorbid older patients aged 70 years or older in Switzerland, Ireland, Belgium and the Netherlands between 2016 and 2019. Data were collected at different time points: admission, discharge, two months post-discharge and one year post-discharge. Atypical antipsychotic prescriptions were classified as appropriate, off-label but accepted, or potentially inappropriate. Outcomes included the prevalence of atypical antipsychotic use at the different time points, deprescribing rates for appropriate and inappropriate prescriptions, and the incidence of new atypical antipsychotic prescriptions among patients not previously treated. Results The number of patients prescribed atypical antipsychotics increased from 88/2005 (4.4%) at admission to 116/1980 (5.9%) at discharge. At admission, 62.5% of these prescriptions were classified as potentially inappropriate. During hospitalisation, 20/53 (37.7%) patients with potentially inappropriate prescriptions either had the medication discontinued or were assigned a new diagnosis that justified the use under an off-label but accepted or otherwise appropriate indication. Additionally, 47 (2.5%) of the 1917 antipsychotic-naïve patients received a new prescription during index admission, with one third (36.2%) lacking a clear indication. Among those newly prescribed atypical antipsychotics without an appropriate indication during hospitalisation, only 58.3% had the medication discontinued within one year of follow-up. Conclusions This study highlights the substantial prevalence of potentially inappropriate atypical antipsychotic prescribing in older multimorbid patients, with no clearly documented indication in almost half of the prescriptions initiated during hospitalisation and slow deprescribing efforts leading to long-term medication risks. Improving prescribing practices through education, protocol-driven deprescribing, and post-discharge follow-up is essential to reduce inappropriate use, and ultimately enhance patient safety.

Long-term prescription of benzodiazepine receptor agonists (BZRAs) for insomnia in adults over 65 years of age is considered a low-value care practice. Although deprescribing has emerged as a possible solution, the implementation of BZRA deprescribing has been considered insufficient in routine clinical care. Mapping care trajectories relative to BZRA deprescribing can help identify inefficiencies in current care and propose strategies to enhance the implementation of deprescribing interventions in the long term. This study aims to map care trajectories and characterise contextual factors relevant to hospital-initiated BZRA deprescribing in older adults. A qualitative study was conducted with local researchers, healthcare professionals (HCPs), patients, and informal carers in six European countries (Belgium, Greece, Norway, Poland, Spain, and Switzerland). Three theoretical frameworks were used to guide data collection and analyses: 1) the '6W' multidimensional model of care trajectories; 2) the patient-centred deprescribing process; and 3) the Context and Capabilities for Integrating Care framework. Data was collected online through self-administered questionnaires, individual interviews, and group validation interviews. Data were transcribed verbatim and analysed using a combination of deductive and inductive thematic analyses. We collected 18 responses to surveys, and conducted 53 interviews (6 local researchers, 36 HCPs, 11 patients or informal carers) and 7 group interviews (comprising 28 HCPs, 4 patients). We developed nine validated care trajectory maps by hospital department and type of unit, and two general comparative maps for inpatient and outpatient care. Hospital-initiated BZRA deprescribing emerged as a complex healthcare process that is likely to involve several HCPs from hospital and primary care. Participants considered patient involvement in shared decision-making (SDM) to be crucial in deprescribing, but implementation was scarce in routine care. The type of HCPs involved and the communication channels between them were specific to each country. Fragmented care and poor communication in the care trajectory hindered follow-up and continuity of care. Deprescribing interventions should include context-sensitive strategies to promote patient participation in SDM, foster the use of guidelines, and enhance interprofessional collaboration along the care trajectory. Care trajectory maps can be used as an implementation tool to translate BZRA deprescribing interventions into routine practice.

Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP. 198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA. In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p<0.0001) with dp-ucMGP levels (β = -0.26, p = 0.045) after integrating effects of height (β = -0.38, p = 0.01), insulin treatment (β = 0.42, p = 0.002), retinopathy treated by laser (β = 0.26, p = 0.02), and total cholesterol levels (β = 0.3, p = 0.03) by multivariable analysis. The association between diabetic neuropathy and the inactive form of MGP suggests the existence of new pathophysiological pathways to explore. Further studies are needed to determine if dp-ucMGP may be used as a biomarker of sensitive neuropathy. Since dp-ucMGP is a marker of poor vitamin K status, clinical studies are warranted to explore the potential protective effect of high vitamin K intake on diabetic peripheral neuropathy.

ObjectivesProton pump inhibitors (PPIs) are widely prescribed medications and commonly used for the treatment of gastric acid-related disorders. Nevertheless, PPIs are often overused leading to potential adverse effects and unnecessary healthcare costs. Deprescribing strategies have emerged to safely reduce or substitute inappropriate PPIs and optimise patient care in an evidence-based manner. This protocol describes a study to evaluate the effectiveness of a PPI deprescribing intervention in comparison to usual care in the Swiss primary care setting.DesignAn open-label, cluster randomised controlled trial.SettingSwiss primary care settings.ParticipantsIncluded participants will be adults with inappropriate PPI treatment and will be recruited by general practitioners (GPs). Participants treated by the same GP constitute a cluster. Clusters are randomised 1:1 to either the intervention group or the control group.InterventionsThe intervention components consist of deprescribing tools including educational material, decision aids for both participants and GPs, and additional trainings for GPs only. Patients in the control group will receive usual care. Data will be collected at baseline, 3-, 6-, 9- and 12-month follow-up time through online surveys or a phone call for both GPs and participants.Primary and secondary outcome measuresThe first co-primary endpoint is the effectiveness of the deprescribing intervention measured by the change of prescribed PPI dose. The second co-primary endpoint is safety, which is measured with the Reflux Disease Questionnaire assessing change in gastrointestinal symptoms. There are several secondary endpoints, such as the total number of prescribed medications, occurrences of changes in prescription patterns, PPI discontinuation and cost-effectiveness.ConclusionsThe findings from this study will provide evidence on the effectiveness and safety of a PPI deprescribing intervention for patients and GPs. Successful implementation of our PPI deprescribing strategy has the potential to improve patient outcomes and lower costs.Trial registration numberNCT06129474.