Quality Improvement Intervention for Reducing Acute Treatment Times in Ischemic Stroke: A Cluster Randomized Clinical Trial

Importance: Efficient care processes are crucial to minimize treatment delays and improve outcome after endovascular thrombectomy (EVT) in patients with ischemic stroke. A potential means to improve care processes is performance feedback. Objective: To evaluate the effect of performance feedback to hospitals on treatment times for EVT. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from January 1, 2020, to June 30, 2022. Participants were consecutive adult patients with ischemic stroke who underwent EVT in 13 Dutch hospitals. No patients were excluded. Data analysis took place from March to May 2023. Intervention: The intervention consisted of feedback on hospital performance using structure, process, and outcome indicators. Indicator scores were based on data from a national quality registry and compared with a benchmark. Performance feedback was provided through a dashboard for local quality improvement teams who developed and implemented improvement plans based on the feedback. Every 6 months, 3 to 4 randomly selected hospitals switched to the intervention condition. Main Outcome and Measures: The primary outcome was time from door to groin puncture for all patients treated with EVT. Secondary outcomes included door-to-needle time, National Institutes of Health Stroke Scale (NIHSS) score at day 2, expanded Treatment in Cerebral Infarction (eTICI) score, and modified Rankin Scale (mRS) score at 3 months. The effect of the intervention was estimated with multivariable linear mixed models. Results: A total of 4747 patients were included (intervention: 2431; control: 2316). Their mean (SD) age was 72 (13) years; 2337 (49.2%) were female and 2410 (50.8%) were male. The median (IQR) baseline NIHSS score was 14 (8-19). Median (IQR) door-to-groin puncture time under the intervention condition was 47 (25-71) minutes, compared with 52 (29-75) minutes under the control condition. The adjusted absolute reduction was 5 minutes (β = -4.8; 95% CI, -9.5 to -0.1; P =.04), corresponding to a relative reduction of 9.2% (95% CI, -18.3% to -0.2%). Conclusion and Relevance: This study found that performance feedback provided through a dashboard used by local quality improvement teams reduced door-to-groin puncture time for EVT. Implementation of performance feedback in hospitals providing EVT can improve the quality of care for ischemic stroke

Characterising the asynchronous resurgence of common respiratory viruses following the COVID-19 pandemic

The COVID-19 pandemic and relevant non-pharmaceutical interventions (NPIs) interrupted the circulation of common respiratory viruses. These viruses demonstrated an unprecedented asynchronous resurgence as NPIs were relaxed. We compiled a global dataset from a systematic review, online surveillance reports and unpublished data from Respiratory Virus Global Epidemiology Network, encompassing 92 sites. We compared the resurgence timings of respiratory viruses within each site and synthesised differences in timings across sites, using a generalised linear mixed-effects model. We revealed a distinct sequential timing in the first post-pandemic resurgence: rhinovirus resurged the earliest, followed by seasonal coronavirus, parainfluenza virus, respiratory syncytial virus, adenovirus, metapneumovirus and influenza A virus, with influenza B virus exhibiting the latest resurgence. Similar sequential timing was observed in the second resurgence except influenza A virus caught up with metapneumovirus. The consistent asynchrony across geographical regions suggests that virus-specific characteristics, rather than location-specific factors, determining the relative timing of resurgence

Do acute postoperative seizures predict epilepsy surgery outcome?: a scoping review

BACKGROUND: Acute postoperative seizures (APOS) are common phenomena following resective epilepsy surgery and can be categorized as running-down (RDS) or running-up seizures (RUS). This differentiation is made retrospectively, considering their classification is based on seizure recurrence. However, early differentiation of RDS from RUS may prevent unnecessary escalation of anti-seizure medication or reoperation. This review provides an overview of the available literature on variables influencing the evolution to RDS/RUS in patients exhibiting acute or early postoperative seizures. METHODS: A database search was performed addressing studies related to the running-down phenomenon and postoperative seizures in PubMed and Embase. Eligibility required a clear definition of acute or early postoperative seizures. Studies concerning any type of epilepsy surgery or pathology were accepted, excluding those related to high-grade malignancies. RESULTS: The search yielded a total of n = 1,690 records. We included n = 21 studies with a total of n = 1,496 patients, which examined variables associated with long-term seizure outcome. Interictal epileptiform discharge presence/laterality, epileptogenic zone size, APOS frequency, and history of generalized tonic-clonic seizures, head trauma, or encephalitis were associated with seizure outcome. Ictal expression and timing of seizure recurrence appeared less relevant. However, these associations are uncertain due to conflicting results between studies, likely due to small sample sizes, a limited reporting of secondary variables, and heterogeneity in study population and methodology. CONCLUSIONS: The variability in clinical outcome following APOS highlights the need for a refined classification of postoperative seizures. Future research should focus on constructing and validating a multifactorial model integrating EEG-derived variables, APOS frequency, and medical history to more accurately predict long-term seizure outcome following resective epilepsy surgery

Vertebral osteomyelitis in patients with infective endocarditis: prevalence, risk factors and mortality

Purpose: Infective endocarditis (IE) can be complicated by vertebral osteomyelitis (VO). This study investigates risk factors associated with VO in patients with infective endocarditis, and 6-month mortality and relapse rates in patients with IE and concomitant VO. Methods: We performed a observational study in two hospitals between September 2016 and October 2022. Patients with possible or definite IE according European Society of Cardiology (2015) modified criteria were retrieved from the local endocarditis team registries. The VO diagnosis was based on radiological signs, irrespective of clinical symptoms. Multivariable logistic regression analysis was performed to identify risk factors for vertebral osteomyelitis. Results: We included 633 consecutive patients with IE. A total of 229 (36.2%) patients had prosthetic valves and 127 (20.1%) had cardiac implantable electronic devices. The most frequent causative micro-organism was Streptococcus species (217, 34.3%), followed by Staphylococcus aureus (167, 26.4%). VO was diagnosed in 73 patients (11.5%, 95% CI 9.0%-14.0%). Enterococcus spp.(OR 2.48, 95% CI 1.31–4.52) and age (OR 1.04 per year, 95% CI 1.02–1.06) were independently associated with concomitant VO. The 6-month mortality risk did not differ between patients with (16/73, 21.9%) or without (110/560, 19.6%) VO (HR 1.13, 95% CI 0.67–1.91). Relapse rate was higher in patients with VO but the difference was not statistically significant (16.1 vs. 7.5%, OR 3.62, 95% CI 0.94–13.34). Conclusions: Twelve percent of patients with IE also had VO. Among older patients and patients with IE caused by enterococci, there should be a higher index of suspicion for vertebral infection

DExD-box RNA helicases in human viral infections: Pro- and anti-viral functions

Viruses have co-evolved with their hosts, intertwining their life cycles. As a result, components and pathways from a host cell's processes are appropriated for virus infection. This review examines the host DExD-box RNA helicases known to influence virus infection during human infections. We have identified 42 species of viruses (28 genera and 21 families) whose life cycles are modulated by at least one, but often multiple, DExD-box RNA helicases. Of these, 37 species require one or multiple DExD-box RNA helicases for efficient infections, i.e., in these cases the DExD-box RNA helicases are pro-viral. However, similar evolutionary processes have also led to cellular responses that combat viral infections. In humans, these responses comprise intrinsic and innate immune responses initiated and regulated by some of the same DExD-box RNA helicases that act as pro-viral helicases. Currently, anti-viral DExD-box RNA helicase responses to viral infections are noted in 23 viral species. Notably, most studied viruses are linked to severe, life-threatening diseases, leading many researchers to focus on DExD-box RNA helicases as potential therapeutic targets. Thus, we present examples of host-directed therapies targeting anti-viral DExD-box RNA helicases. Overall, our findings indicate that various DExD-box RNA helicases serve as either pro- and/or anti-viral agents across a wide range of viruses. Continued investigation into the pro-viral activities of these helicases will help identify specific protein motifs that can be targeted by drugs to manage or eliminate the severe diseases caused by these viruses. Comparative studies on anti-viral DExD-box RNA helicase responses may also offer insights for developing therapies that enhance immune responses triggered by these helicases

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes. Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 106 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1. Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing. Findings: Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and –1·5 (95% CI –5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI –1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care. Interpretation: Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease. Funding: Janssen Research & Development, Legend Biotech USA