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Background: We previously performed a pragmatic cluster randomized controlled trial (RCT) in general practices and older adult care organizations in Poland, the Netherlands, Norway, and Sweden. We found that a multifaceted antibiotic stewardship intervention (ASI) substantially reduced antibiotic use for suspected urinary tract infections (UTIs) in frail older adults compared with usual care. We aimed to evaluate the implementation process of the ASI to provide recommendations for clinical practice. Methods: We conducted a process evaluation alongside the cluster RCT. The ASI consisted of a decision-tool and a toolbox, which were implemented using a participatory-action-research (PAR) approach with sessions for education and evaluation. We documented the implementation process of the intervention and administered a questionnaire to health care professionals (HCPs) from participating organizations in the intervention and usual care clusters. We evaluated the multiple components of the intervention and its implementation following a structured framework. Results: The questionnaire was completed by 254 HCPs from the 38 participating clusters. All components were largely delivered according to plan and evaluated as useful. The decision-tool and toolbox materials were reported to facilitate decision-making on UTIs. Regarding the PAR approach, educational sessions focusing on the distinction between UTIs and asymptomatic bacteriuria were held in all 19 intervention clusters. In 17 out of these 19 clusters, evaluation sessions took place, which were reported to help remind HCPs to implement the ASI. During both sessions, HCPs valued the reflection that took place and the resulting awareness of their behavior. It allowed them to explore implementation barriers and to tailor their local implementation process to overcome these. For example, HCPs organized extra educational sessions or revised local policies to incorporate the use of the decision-tool. Various HCPs took key roles in implementation. Staff changes and the COVID-19 pandemic were important contextual barriers. Conclusions: We found each component of the multifaceted ASI and its implementation to have added value in the process to improve antibiotic prescribing for suspected UTIs in a heterogeneous older adult care setting. We recommend using a multifaceted, multidisciplinary approach that enables HCPs to reflect on their current practice and accordingly tailor local implementation. Trial registration: ClinicalTrials.gov NCT03970356. Registered on May 31, 2019. [ABSTRACT FROM AUTHOR]

Background a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. Objectives (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. Methods we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. Results participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. Conclusions decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions. [ABSTRACT FROM AUTHOR]

Objective. To determine the genotype-phenotype association in patients with adenosine deaminase-2 (ADA2) deficiency due to identical homozygous R169Q mutations in CECR1. Methods. We present a case series of nine ADA2-deficient patients with an identical homozygous R169Q mutation. Clinical and diagnostic data were collected and available MRI studies were reviewed. We performed genealogy and haplotype analyses and measured serum ADA2 activity. ADA2 activity values were correlated to clinical symptoms. Results. Age of presentation differed widely between the nine presented patients (range: 0 months to 8 years). The main clinical manifestations were (hepato)splenomegaly (8/9), skin involvement (8/9) and neurological involvement (8/9, of whom 6 encountered stroke). Considerable variation was seen in type, frequency and intensity of other symptoms, which included aplastic anaemia, acute myeloid leukaemia and cutaneous ulcers. Common laboratory abnormalities included cytopenias and hypogammaglobulinaemia. ADA2 enzyme activity in patients was significantly decreased compared with healthy controls. ADA2 activity levels tended to be lower in patients with stroke compared with patients without stroke. Genealogical studies did not identify a common ancestor; however, based on allele frequency, a North-West European founder effect can be noted. Three patients underwent haematopoietic cell transplantation, after which ADA2 activity was restored and clinical symptoms resolved. Conclusion. This case series revealed large phenotypic variability in patients with ADA2 deficiency though they were homozygous for the same R169Q mutation in CECR1. Disease modifiers, including epigenetic and environmental factors, thus seem important in determining the phenotype. Furthermore, haematopoietic cell transplantation appears promising for those patients with a severe clinical phenotype. [ABSTRACT FROM AUTHOR]