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Aims Many clinical decision support systems trigger warning alerts for drug-drug interactions potentially leading to QT prolongation and torsades de pointes (QT-DDIs). Unfortunately, there is overalerting and underalerting because stratification is only based on a fixed QT-DDI severity level. We aimed to improve QT-DDI alerting by developing and validating a risk prediction model considering patient- and drug-related factors. Methods We fitted 31 predictor candidates to a stepwise linear regression for 1000 bootstrap samples and selected the predictors present in 95% of the 1000 models. A final linear regression model with those variables was fitted on the original development sample (350 QT-DDIs). This model was validated on an external dataset (143 QT-DDIs). Both true QTc and predicted QTc were stratified into three risk levels (low, moderate and high). Stratification of QT-DDIs could be appropriate (predicted risk = true risk), acceptable (one risk level difference) or inappropriate (two risk levels difference). Results The final model included 11 predictors with the three most important being use of antiarrhythmics, age and baseline QTc. Comparing current practice to the prediction model, appropriate stratification increased significantly from 37% to 54% appropriate QT-DDIs (increase of 17.5% on average [95% CI +5.4% to +29.6%], padj = 0.006) and inappropriate stratification decreased significantly from 13% to 1% inappropriate QT-DDIs (decrease of 11.2% on average [95% CI −17.7% to −4.7%], padj ≤ 0.001). Conclusion The prediction model including patient- and drug-related factors outperformed QT alerting based on QT-DDI severity alone and therefore is a promising strategy to improve DDI alerting.

OBJECTIVES: To date, pain relief in general continues to be the most prominent outcome measurement in daily routine care and clinical research. Nevertheless, the awareness of a shift toward more functional outcomes and/or emotional and cognitive outcomes has been raised. The interplay between bodily functions (such as pain intensity) and emotional or cognitive factors, however, has not yet been fully elucidated. The aim of this study was to systematically review the evidence for associations between bodily functions and cognitive and emotional factors in patients with chronic pain who are treated with neuromodulation. MATERIALS AND METHODS: Four data bases were consulted for this systematic literature review: PubMed, Web of Science, Scopus, and Embase. The Downs and Black Checklist (modified) was used to assess the risk of bias. The study protocol was prospectively registered at the International prospective register of systematic reviews (PROSPERO, CRD42021226803). If two or more studies reported correlation coefficients for a specific association, a meta-analysis based on correlation coefficients was performed for that specific association. RESULTS: The initial data base search identified a total of 1432 studies, of which 19 studies were eventually included in the systematic review. Evidence was found for two associations: 1) a positive correlation between pain intensity and anxiety (r = 0.42; 95% CI, 0.34 to 0.50) and 2) a positive correlation between pain intensity and depression (r = 0.32; 95% CI, 0.10 to 0.51). The association between pain intensity and catastrophizing was not statistically significant (r = 0.23; 95% CI, -0.36 to 0.69). CONCLUSIONS: On the basis of the associations between pain intensity and anxiety/depression, a biopsychosocial approach might be the most suitable in clinical practice to properly address all aspects of the International Classification of Functioning, Disability, and Health framework in patients who are treated with neuromodulation.

OBJECTIVES: Spinal cord stimulation (SCS) can reduce the need for opioids; however, the influence on the full spectrum of pain medication is less known. The aims of this study were to explore general prescription practices for patients scheduled for SCS, potential differences in prescriptions between Belgium and United Kingdom, and the influence of SCS on pain medication. MATERIALS AND METHODS: Individual patient data from the TRIAL-STIM study in the United Kingdom and DISCOVER in Belgium were pooled. Medication use was collected before SCS and three months after SCS from 180 chronic pain patients. The Medication Quantification Scale III (MQS) was used to calculate a total score for medication use, as well as subscores for several classes. Differences in prescription practices between United Kingdom and Belgium were evaluated with two-sided Wilcoxon tests. To evaluate differences in medication use after three months of SCS between United Kingdom and Belgium, Tweedie-generalized linear models were calculated.RESULTS: There was a statistically significant difference (-6.40 [95% CI from -3.40 to -9.10]) between the median total MQS score in United Kingdom and Belgium before SCS. Additionally, a significant difference was found for nonsteroidal anti-inflammatory drugs (NSAIDs) (-3.40 [95% CI -3.40 to -6.80]), neuropathic agents (-2.30 [95% CI -0.40 to -3.80]), and benzodiazepines (1.83e-05 [95% CI 2.64-05 to 7.45-05 ]) between United Kingdom and Belgium, before SCS. Tweedie-generalized models revealed a statistically significant interaction between country and time for MQS, neuropathic agents, and opioids. CONCLUSIONS: Our combined analysis revealed differences in prescription practice in patients scheduled for SCS implantation between Belgium and United Kingdom. NSAIDs and neuropathic mood agents are more frequently used in the United Kingdom, presumably due to easier access to repeat prescriptions and over the counter medications. After three months of SCS, a decrease in medication use is observed in both countries, with higher reductions in Belgium, presumably due to strict regulations concerning reimbursement criteria.

AIM: After preterm birth, supine head midline position is supported for stable cerebral blood flow (CBF) and prevention of intraventricular haemorrhage (IVH), while prone position supports respiratory function and enables skin-to-skin care. The prone compared to supine position could lead to a change in near-infrared derived cerebral tissue oxygen saturation (rScO2), which is a surrogate for cerebral blood flow (CBF). By monitoring rScO2 neonatologists aim to stabilise CBF during intensive care and prevent brain injury. In this systematic review and meta-analysis, we investigate the effect of the body position on rScO2. METHODS: A comprehensive literature search was performed to identify all trials that included preterm infants in the first 2 weeks after birth and compared rScO2 in the prone versus supine head in midline position of the infant. A meta-analysis, including two subgroup analyses based on postnatal age (PNA) and gestational age (GA), was performed. RESULTS: Six observational cohort studies wereincluded. In the second, but not the first week after birth, a significant higher rScO2 in the prone position was found with a mean difference of 1.97% (95% CI 0.87-3.07). No rScO2 difference was observed between positions in the extremely preterm nor the preterm group. CONCLUSION: No consistent evidence was found that body position influences rScO2 in the first 2 weeks after preterm birth. Subgroup analysis suggests that in the second week after birth, the prone position might result in higher cerebral rScO2 than the supine position with head in midline. Multiple factors determine the best body position in preterms.

Introduction Apart from the clinical efficacy of high frequency spinal cord stimulation at 10 kHz, the underlying mechanism of action remains unclear. In parallel with spinal or segmental theories, supraspinal hypotheses have been recently proposed. In order to unveil hidden altered brain connectome patterns, a resting state functional magnetic resonance imaging (rsfMRI) protocol was performed in subjects routinely treated for back and/or leg pain with high-frequency spinal cord stimulation (HF-SCS) HF-SCS at 10 kHz. Methods RsfMRI imaging was obtained from ten patients with failed back surgery syndrome who were eligible for HF-SCS at 10 kHz. Specifically-chosen regions of interest with different connectivity networks have been investigated over time. Baseline measurements were compared with measurements after 1 month and 3 months of HF-SCS at 10 kHz. Additionally, clinical parameters on pain intensity, central sensitization, pain catastrophizing, and sleep quality were correlated with the functional connectivity strengths. Results The study results demonstrate an increased connectivity over time between the anterior insula (affective salience network) and regions of the frontoparietal network and the central executive network. After 3 months of HF-SCS, the increased strength in functional connectivity between the left dorsolateral prefrontal cortex and the right anterior insula was significantly correlated with the minimum clinically important difference (MCID) value of the Pittsburgh sleep quality index. Conclusion These findings support the hypothesis that HF-SCS at 10 kHz might influence the salience network and therefore also the emotional awareness of pain.

In-ambulance telemedicine for stroke (telestroke) is a promising concept. Real-time bidirectional audiovisual communication between a patient in a moving ambulance and a remote stroke expert can facilitate specialized care at a very early stage. We have developed several prototypes for in-ambulance telemedicine and we have created a telemedicine platform encompassing standardized assessment of stroke severity using the Unassisted TeleStroke Scale (UTSS), clinical decision support software for stroke physicians and reporting functionality for the in-hospital team awaiting the patient. Feasibility studies using this system in healthy volunteers and in patients during paramedic emergency missions have shown that this approach is safe, feasible and well-accepted by all stakeholders. We have completed a pilot study on 24/7 in-ambulance telestroke support, confirming the safety, feasibility and reliability of this concept.We present a video fragment of an in-ambulance teleconsultation from this trial.Already during patient evacuation to the ambulance, vital data was exchanged between the general practitioner present at the location and the remote stroke physician. During emergency transportation to the hospital, the teleconsultant examined the patient, alarmed the in-hospital team and communicated critical information to the in-hospital team (patient identification and date of birth, vital parameters, glycaemia, time of symptom onset, stroke severity based on the UTSS, Glasgow Coma Scale score, medical history, concomitant medication, suspected diagnosis, checklist for treatment with intravenous thrombolysis, family contact information, premorbid modified Rankin Scale score). A single-center randomized clinical trial evaluating the efficacy, safety, feasibility, reliability, and cost-effectiveness of in-ambulance telestroke is currently ongoing.

Dabigatran etexilate is emerging as an alternative for vitamin K antagonists, but evidence-based guidelines for management of intracerebral hemorrhage and acute ischemic stroke in patients taking this drug are nonexistent. This review summarizes current knowledge on key pharmacological features and the assessment of dabigatran activity. Pragmatic approaches are provided for individualized decision taking with regard to hemostatic therapy and reperfusion strategies in acute stroke patients.