Evaluation of early implementations of antibiotic stewardship program initiatives in nine Dutch hospitals

Background Antibiotic resistance is a global threat to patient safety and care. In response, hospitals start antibiotic stewardship programs to optimise antibiotic use. Expert-based guidelines recommend strategies to implement such programs, but local implementations may differ per hospital. Earlier published assessments determine maturity of antibiotic stewardship programs based on expert-based structure indicators, but they disregard that there may be valid deviations from these expert-based programs. Aim To analyse the progress and barriers of local implementations of antibiotic stewardship programs with stakeholders in nine Dutch hospitals and to develop a toolkit that guides implementing local antibiotic stewardship programs. Methods An online questionnaire based on published guidelines and recommendations, conducted with seven clinical microbiologists, seven infectious disease physicians and five clinical pharmacists at nine Dutch hospitals. Results Results show local differences in antibiotic stewardship programs and the uptake of interventions in hospitals. Antibiotic guidelines and antibiotic teams are the most extensively implemented interventions. Education, decision support and audit-feedback are deemed important interventions and they are either piloted in implementations at academic hospitals or in preparation for application in non-academic hospitals. Other interventions that are recommended in guidelines - benchmarking, restriction and antibiotic formulary - appear to have a lower priority. Automatic stop-order, pre-authorization, automatic substitution, antibiotic cycling are not deemed to be worthwhile according to respondents. Conclusion There are extensive local differences in the implementation of antibiotic stewardship interventions. These differences suggest a need to further explore the rationale behind the choice of interventions in antibiotic stewardship programs. Rather than reporting this rationale, this study reports where rationale can play a key role in the implementation of antibiotic stewardship programs. A one-size-fits-all solution is unfeasible as there may be barriers or valid reasons for local experts to deviate from expert-based guidelines. Local experts can be supported with a toolkit containing advice based on possible barriers and considerations. These parameters can be used to customise an implementation of antibiotic stewardship programs to local needs (while retaining its expert-based foundation)

Participatory eHealth development to support nurses in antimicrobial stewardship

Background Antimicrobial resistance poses a threat to patient safety worldwide. To stop antimicrobial resistance, Antimicrobial Stewardship Programs (ASPs; programs for optimizing antimicrobial use), need to be implemented. Within these programs, nurses are important actors, as they put antimicrobial treatment into effect. To optimally support nurses in ASPs, they should have access to information that supports them in their preparation, administration and monitoring tasks. In addition, it should help them to detect possible risks or adverse events associated with antimicrobial therapy. In this formative study, we investigate how nurses’ can be supported in ASPs by means of an eHealth intervention that targets their information needs. Methods We applied a participatory development approach that involves iterative cycles in which health care workers, mostly nurses, participate. Focus groups, observations, prototype evaluations (via a card sort task and a scenario-based information searching task) and interviews are done with stakeholders (nurses, managers, pharmacist, and microbiologist) on two pulmonary wards of a 1000-bed teaching hospital. Results To perform the complex antimicrobial-related tasks well, nurses need to consult various information sources on a myriad of occasions. In addition, the current information infrastructure is unsupportive of ASP-related tasks, mainly because information is not structured to match nurse tasks, is hard to find, out of date, and insufficiently supportive of awareness. Based our findings, we created a concept for a nurse information application. We attuned the application’s functionality, content, and structure to nurse work practice and tasks. Conclusions By applying a participatory development approach, we showed that task support is a basic need for nurses. Participatory development proved useful regarding several aspects. First, it allows for combining bottom-up needs (nurses’) and top-down legislations (medical protocols). Second, it enabled us to fragmentise and analyse tasks and to reduce and translate extensive information into task-oriented content. Third, this facilitated a tailored application to support awareness and enhance patient safety. Finally, the involvement of stakeholders created commitment and ownership, and helped to weigh needs from multiple perspective

Bacterium-like particles as multi-epitope delivery platform for Plasmodium berghei circumsporozoite protein induce complete protection against malaria in mice

Contains fulltext : 110364.pdf (publisher's version ) (Open Access)BACKGROUND: Virus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins. The present study reports the immunogenicity and protective efficacy of bacterium-like particles (BLPs) generated from Lactococcus lactis and loaded with Plasmodium berghei circumsporozoite protein (PbCSP) peptides. METHODS: A panel of BLP-PbCSP formulations differing in composition and quantity of B-cell, CD4+ and CD8+ T-cell epitopes of PbCSP were tested in BALB/c mice. RESULTS: BLP-PbCSP1 induced specific humoral responses but no IFN-gamma ELISPOT response, protecting 30-40% of the immunized mice. BLP-PbCSP2, with reduced length of the non-immunogenic part of the T-cell-epitopes construct, increased induction of IFN-gamma responses as well as protection up to 60-70%. Compared to controls, lower parasitaemia was observed in unprotected mice immunized with BLP-PbCSP1 or 2, suggestive for partial immunity. Finally, further increase of the number of B-cell epitopes and codon optimization (BLP-PbCSP4) induced the highest anti-CSP antibody levels and number of IFN-gamma spots, resulting in sterile immunity in 100% of the immunized mice. CONCLUSION: Presentation of Plasmodium-derived antigens using BLPs as a delivery system induced complete protection in a murine malaria model. Eventually, BLPs have the potential to be used as a novel versatile delivery platform in malaria vaccine development

Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial

BACKGROUND AND PURPOSE: Body temperature is a strong predictor of outcome in acute stroke. However, it is unknown whether antipyretic treatment leads to early and clinically worthwhile reduction of body temperature in patients with acute stroke, especially when they have no fever. The main purpose of this trial was to study whether early treatment of acute ischemic stroke patients with acetaminophen (paracetamol) reduces body temperature. METHODS: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 500 mg (low dose) or 1000 mg (high dose) acetaminophen or with placebo, administered as suppositories 6 times daily during 5 days. Body temperatures were measured with a rectal electronic thermometer at the start of treatment and after 24 hours and with an infrared tympanic thermometer at 2-hour intervals during the first 24 hours and at 6-hour intervals thereafter. The primary outcome measure was rectal temperature at 24 hours after the start of treatment. RESULTS: Treatment with high-dose acetaminophen resulte

Measuring affective state:Subject-dependent and-independent prediction based on longitudinal multimodal sensing

Current sensors offering passive and continuous monitoring of behavioral patterns potentially enable real-time affective state monitoring. Previous research on affective state prediction with multimodal sensing in daily life has shown only small-to-moderate effects. One reason for this limited success might be the large variability across individuals. Current research is often of short duration, preventing proper within-individual modeling. With an extensive longitudinal data collection of nine months, this research focuses on individual-level predictions of valence and arousal in daily life. Sixteen PhD candidates from The Netherlands provided data about their affective states (self-reported valence and arousal), physiology (Oura rings) and behavioral patterns (AWARE framework for mobile phone data). Supporting our hypothesis, subject-dependent random forest (RF) models significantly outperformed subject-independent leave-one-subject-out (LOSO) models in predicting self-reported valence and arousal. The subject-dependent models achieved an average Spearman's rho correlation of 0.30 [0.14-0.60] for valence and 0.36 [0.16-0.69] for arousal. In many cases, participants' a priori indicated informative sources matched with the feature importance. Making use of participants' self-knowledge might thus help to reduce the amount of data to be collected. For future work, longer-term changes in affective state and combinations of features for estimating real behavioral patterns should be explored.</p

Towards continuous mental state detection in everyday settings: investigating between-subjects variations in a longitudinal study

Maintaining mental health can be quite challenging, especially when exposed to stressful situations. In many cases, mental health problems are recognized too late to effectively intervene and prevent adverse outcomes. Recent advances in the availability and reliability of wearable technologies offer opportunities for continuously monitoring mental states, which may be used to improve a person’s mental health. Previous studies attempting to detect and predict mental states with different modalities have shown only small to moderate effect sizes. This limited success may be due to the large variability between individuals regarding e.g., ways of coping with stress or behavioral patterns associated with positive or negative feelings. A study was set up for the detection of mental states based on longitudinal wearable and contextual sensing, targeted at investigating between-subjects variations in terms of predictors of mental states and variations in how predictors relate to mental states. At the end of March 2022, 16 PhD candidates from the Netherlands started to participate in the study. Over nine months, we collected data in terms of their daily mental states (valence and arousal), continuous physiological data (Oura ring) and smartphone data (AWARE framework including GPS and smartphone usage). From the raw data, we aggregated daily values for each participant in terms of sleep, physical activity, mental states, phone usage and GPS movement. First results (six months into the study at the time of writing) indicate that almost all participants show a large variability in ratings of daily mental states, which is a prerequisite for predictive modeling. Direction, strength and standard deviations of Spearman correlations between valence, arousal and the different variables suggest that several predictors of valence and arousal are more subject dependent than others. In future analyses, we will test and compare different versions of predictive modeling to highlight the potential of wearable technologies for mental state monitoring and the personalized prediction of the development of mental problems

The Association of Early Electrocardiographic Abnormalities With Brain Injury Severity and Outcome in Severe Traumatic Brain Injury

The aim of this study was to evaluate the frequency of electrocardiographic (ECG) abnormalities in the acute phase of severe traumatic brain injury (TBI) and the association with brain injury severity and outcome. In contrast to neurovascular diseases, sparse information is available on this issue. Data of adult patients with severe TBI admitted to the Intensive Care Unit (ICU) for intracranial pressure monitoring of a level-1 trauma center from 2002 till 2018 were analyzed. Patients with a cardiac history were excluded. An ECG recording was obtained within 24 h after ICU admission. Admission brain computerized tomography (CT)-scans were categorized by Marshall-criteria (diffuse vs. mass lesions) and for location of traumatic lesions. CT-characteristics and maximum Therapy Intensity Level (TILmax) were used as indicators for brain injury severity. We analyzed data of 198 patients, mean (SD) age of 40 +/- 19 years, median GCS score 3 [interquartile range (IQR) 3-6], and 105 patients (53%) had thoracic injury. In-hospital mortality was 30%, with sudden death by cardiac arrest in four patients. The incidence of ECG abnormalities was 88% comprising ventricular repolarization disorders (57%) mostly with ST-segment abnormalities, conduction disorders (45%) mostly with QTc-prolongation, and arrhythmias (38%) mostly of supraventricular origin. More cardiac arrhythmias were observed with increased grading of diffuse brain injury (p = 0.042) or in patients treated with hyperosmolar therapy (TILmax) (65%, p = 0.022). No association was found between ECG abnormalities and location of brain lesions nor with thoracic injury. Multivariate analysis with baseline outcome predictors showed that cardiac arrhythmias were not independently associated with in-hospital mortality (p = 0.097). Only hypotension (p = 0.029) and diffuse brain injury (p = 0.017) were associated with in-hospital mortality. In conclusion, a high incidence of ECG abnormalities was observed in patients with severe TBI in the acute phase after injury. No association between ECG abnormalities and location of brain lesions or presence of thoracic injury was present. Cardiac arrhythmias were indicative for brain injury severity but not independently associated with in-hospital mortality. Therefore, our findings likely suggest that ECG abnormalities should be considered as cardiac mimicry representing the secondary effect of traumatic brain injury allowing for a more rationale use of neuroprotective measures

Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]

BACKGROUND: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. METHODS: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. RESULTS: No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3°C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 °C). Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. CONCLUSIONS: Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome

Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]

BACKGROUND: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. METHODS: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. RESULTS: No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3°C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 °C). Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. CONCLUSIONS: Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome