Multicenter Evaluation Research Articles

The implementation of an electronic symptom management system to monitor postoperative pain in gynecologic oncology surgery patients: A multicenter evaluation

The implementation of an electronic symptom management system to monitor postoperative pain in gynecologic oncology surgery patients: A multicenter evaluation

The implementation of an electronic symptom management system to monitor the severity of symptoms in gynecologic oncology patients initiating chemotherapy: A multicenter evaluation

The implementation of an electronic symptom management system to monitor the severity of symptoms in gynecologic oncology patients initiating chemotherapy: A multicenter evaluation

Efficacy of a gelling-fibre dressing and a gelling-fibre dressing with silver nanoparticles at controlling exudate and infection: a 4-week multicentre clinical evaluation.

Suprasorb Liquacel Pro (standard test dressing) and Suprasorb Liquacel Ag (test dressing with silver nanoparticles) are absorptive gelling-fibre dressings designed to manage wound exudate levels and promote moist wound healing, with the latter having additional antimicrobial properties. To assess the impact of the test dressing on healing, exudate levels and signs of infection. Patients with moderately-to-highly exuding hard-to-heal wounds of any type were dressed with the standard test dressing or the test dressing with silver nanoparticles if they showed covert or overt signs of local infection. Comparative data were collected at baseline and 4-week conclusion. Adverse events and patient and professional opinions were also reported and collated. There were 19 patients with lower-limb wounds of various types present for a mean of 26 months. At baseline, most wounds were deteriorating or static (68%), while at conclusion most were improving or healed (84%), with additional indicators of improved healing. The number of patients with moderate-to-high exudate levels decreased from 84% to 53%. The 15 patients using the test dressing with silver nanoparticles saw reductions in covert signs of infection from 93% to 80%, overt signs of infection from 33% to 13% and antibiotic use from 13% to 7%. On average, the test dressings were effective in managing and reducing the barriers to healing, including high exudate, infection and biofilm, and in restarting stalled healing.

Multicenter evaluation of patient safety incidents in lung surgery: The EPSI study

Multicenter evaluation of patient safety incidents in lung surgery: The EPSI study

Multigeographic clinical assessment of a molecular diagnostic assay for detection of key codons to predict decreased susceptibility or resistance to cephalosporins in Neisseria gonorrhoeae.

Cephalosporin resistance in Neisseria gonorrhoeae has severely compromised the efficacy of World Health Organization (WHO)-recommended therapies. This study aimed to methodologically evaluate the optimized Six-CodonPlus assay, and additionally conducted a multicenter evaluation to assess its clinical application, especially for predicting antimicrobial resistance (AMR). For methodological evaluation, 397 sequence-known N. gonorrhoeae isolates were evaluated for specificity, 17 nongonococcal isolates were assessed for cross-reactivity, 159 uncultured urogenital swabs and urine samples were evaluated for sensitivity at the clinical level. For multicenter evaluation, 773 isolates with confirmed phenotypic data and 718 clinical urogenital swabs collected from four geographical cities were, respectively, utilized for the evaluation of AMR-prediction strategies and the clinical application of the assay. The assay accurately identified specific single-nucleotide polymorphisms in resistance-associated genes, the detection limits dropped to 10 copies/reaction for individual targets. The specificity reached 100% and no cross-reactivity occurred with double-target confirmation. The assay could be directly applied to clinical samples containing over 20 copies/reaction. Multicenter evaluation formulated two optimal strategies for decreased susceptibility prediction in specific scenarios, and one tactic for prediction of resistance and identification of FC428-like strains. High sensitivity of 86.84% (95% CI, 71.11-95.05) and specificity of 99.59% (95% CI, 98.71-99.89) for resistance prediction were demonstrated for ceftriaxone (CRO). Regarding N. gonorrhoeae identification among multicenter swabs, specificity reached 97.53% (95% CI, 95.49-98.69), and sensitivity reached 93.77% (95% CI, 90.04-96.22). The Six-CodonPlus assay exhibited excellent detection performance and formulated optimal AMR-related prediction strategy with regional adaptability, providing critical information for population screening and clinical treatment.

Cardiovascular emergency in indonesian primary health care (PUSKESMAS): a national multicentre service evaluation study based on ESC guidelines adherence

Abstract Background Early diagnosis and prompt treatment are crucial in reducing cardiovascular (CVD) burden in the global level, especially in Indonesia with more than a half million CVD death annually. As frontliner, more than 10,000 primary healthcare (PUSKESMAS) spreading around Indonesia are pivotal in delivering CVD emergency care. However, due to the scarcity of healthcare resources, significant disparities exist between guideline recommendations and their implementation in Indonesian primary health care. Purpose Our study aims to describe current cardiovascular emergency care, assess guideline adherence, and identify key factors influencing the trend. Methods This multicentre study was conducted in 40 PUSKESMAS across Indonesia from October to December 2023. Data related to cardiovascular emergencies diagnosis, work-ups, treatment, and outcomes were gathered and then evaluated according to the ESC Guidelines. Recommendations, particularly Class I, were converted into points with respect to diagnostic and treatment domains. Guideline adherence scores were then calculated based on the percentage of accomplished points. Linear regression analysis was employed to identify factors that could explain variations in guideline adherence across all PUSKESMAS. Results 215 CVD emergency patients were reported. The most prevalent diagnosis was hypertensive crisis (n=137; 64%) with ECG done in only 26% of cases and none underwent imaging. Oral amlodipine (59%) and captopril (55%) were mostly used as antihypertensive, with none receiving intravenous. The second most common diagnosis was ACS (n=42; 20%), with ECG performed in only 71% of cases. Among 13 patients with STEMI, 69% only received aspirin, and 46% were given DAPT. Malignant arrhythmia occurred in 26 patients, with none receiving cardioversion. The most used anti-arrhythmic are bisoprolol, propranolol, and atropine. Among 23 cases of acute HF, only 39% received oxygen, while IV furosemide was used in only one case. Cardiac arrest occurred in two patients, both received CPR and epinephrine. In terms of guideline adherence, mean diagnostic score (%) was demonstrated highest in Cardiac Arrest at 100 and the lowest in Hypertensive Crisis and Acute HF at 53, while mean treatment score (%) was highest in Hypertensive Crisis at 86 and lowest in arrhythmia at 25. Linear regression suggests that human resources have a positive and significant association with diagnostic adherence scores (R2: 0.3485, p-value: 0.0450), whereas essential medicine has a strong but non-significant correlation with treatment adherence score (R2: 1.0768, p-value: 0.460). Conclusion This study has demonstrated a huge disparity between the current CVD emergency practices and guidelines in Indonesian primary healthcare. These gaps emphasised the need for improved human resources and essential medicine for primary healthcare along with the implementation of data-driven policy making concerning cardiovascular disease in Indonesia.Cardiovascular Emergency Diagnosis in InCardiovascular Emergency Work-up and Tre

Optimizing patient selection for cardiac resynchronization therapy in a multicenter study of Japanese patients: assessment of the MADIT-ICD benefit group

Abstract Background The MADIT-ICD benefit group, derived from ventricular tachycardia (VT)/ventricular fibrillation (VF) scores and non-arrhythmic mortality scores (Table 1), facilitates the appropriate selection of candidates for implantable cardioverter-defibrillator (ICD) therapy. While the 2021 European Society of Cardiology Guidelines have discussed the advantages and considerations of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT), the optimal selection of CRT with or without a defibrillator remains unclear, particularly in Asian populations. This is especially relevant for primary prevention using ICD, which is characterized by fewer cases of ischemic etiology compared to Western countries. Purpose This study aimed to evaluate the utility of the MADIT-ICD benefit group in Japanese CRT patients and identify key indicators for determining the necessity of CRT with or without a defibrillator. Methods We conducted a retrospective, multicenter evaluation of 505 consecutive Japanese CRT patients enrolled between 2012 and 2020. Among these patients, 76% were male, with a mean age of 65 years and a mean body mass index of 22.5 kg/m2. Ischemic etiology was present in 25% of patients, with 20% undergoing secondary prevention. The study assessed the cumulative incidences of VT/VF and non-arrhythmic mortality based on the MADIT-ICD benefit group (lowest, intermediate, and highest). Predictors for each outcome were explored, and the MADIT-ICD benefit group was validated in the Japanese cohort. Results Of the 400 included patients, 60 (15%) were categorized into the lowest MADIT-ICD benefit group, 279 (70%) into the intermediate group, and 61 (15%) into the highest group. Over a median follow-up period of 34 months, VT/VF occurred in 4 (13%), 68 (24%), and 14 (23%) patients in the lowest, intermediate, and highest benefit groups, respectively (Gray’s test, P = 0.027, Figure 1A). Non-arrhythmic death occurred in 15 (25%), 91 (33%), and 9 (15%) patients in the lowest, intermediate, and highest benefit groups, respectively (Log-rank test, P = 0.025, Figure 1B). Multivariable analysis identified MADIT-ICD VT/VF score (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.12-1.35; P < 0.001) and left bundle branch block (LBBB) (HR 0.48; 95% CI 0.27-0.86; P = 0.014) as significant predictors for VT/VF, while MADIT-ICD non-arrhythmic mortality score (HR 1.16; 95% CI 1.07-1.27; P < 0.001), serum creatinine (Cr) (HR 1.28; 95% CI 1.13-1.45; P < 0.001), and mineral corticoid receptor antagonist (MRA) use (HR 1.84; 95% CI 1.21-2.79; P = 0.004) were significant predictors for non-arrhythmic death (Table 2). Conclusion The MADIT-ICD benefit group, in conjunction with left bundle branch block and renal function, may serve as valuable predictors for determining the necessity of cardioverter-defibrillator therapy in Japanese CRT patients.Table 1 and Figure 1

Privacy enhancing and generalizable deep learning with synthetic data for mediastinal neoplasm diagnosis

The success of deep learning (DL) relies heavily on training data from which DL models encapsulate information. Consequently, the development and deployment of DL models expose data to potential privacy breaches, which are particularly critical in data-sensitive contexts like medicine. We propose a new technique named DiffGuard that generates realistic and diverse synthetic medical images with annotations, even indistinguishable for experts, to replace real data for DL model training, which cuts off their direct connection and enhances privacy safety. We demonstrate that DiffGuard enhances privacy safety with much less data leakage and better resistance against privacy attacks on data and model. It also improves the accuracy and generalizability of DL models for segmentation and classification of mediastinal neoplasms in multi-center evaluation. We expect that our solution would enlighten the road to privacy-preserving DL for precision medicine, promote data and model sharing, and inspire more innovation on artificial-intelligence-generated-content technologies for medicine.

A multicenter evaluation of a novel microfluidic rapid AST assay for Gram-negative bloodstream infections.

Increasing antimicrobial resistance underscores the need for new diagnostic solutions to guide therapy, but traditional antimicrobial susceptibility testing (AST) is often inadequate in time-critical diseases such as sepsis. This work presents a novel and rapid AST system with a rapid turnaround of results, which may help reduce the time to guided therapy, possibly allowing early de-escalation of broad-spectrum empirical therapy as well as rapid adjustments to treatments when coverage is lacking.

A multicenter study on deep learning for glioblastoma auto-segmentation with prior knowledge in multimodal imaging.

A precise radiotherapy plan is crucial to ensure accurate segmentation of glioblastomas (GBMs) for radiation therapy. However, the traditional manual segmentation process is labor-intensive and heavily reliant on the experience of radiation oncologists. In this retrospective study, a novel auto-segmentation method is proposed to address these problems. To assess the method's applicability across diverse scenarios, we conducted its development and evaluation using a cohort of 148 eligible patients drawn from four multicenter datasets and retrospective data collection including noncontrast CT, multisequence MRI scans, and corresponding medical records. All patients were diagnosed with histologically confirmed high-grade glioma (HGG). A deep learning-based method (PKMI-Net) for automatically segmenting gross tumor volume (GTV) and clinical target volumes (CTV1 and CTV2) of GBMs was proposed by leveraging prior knowledge from multimodal imaging. The proposed PKMI-Net demonstrated high accuracy in segmenting, respectively, GTV, CTV1, and CTV2 in an 11-patient test set, achieving Dice similarity coefficients (DSC) of 0.94, 0.95, and 0.92; 95% Hausdorff distances (HD95) of 2.07, 1.18, and 3.95 mm; average surface distances (ASD) of 0.69, 0.39, and 1.17 mm; and relative volume differences (RVD) of 5.50%, 9.68%, and 3.97%. Moreover, the vast majority of GTV, CTV1, and CTV2 produced by PKMI-Net are clinically acceptable and require no revision for clinical practice. In our multicenter evaluation, the PKMI-Net exhibited consistent and robust generalizability across the various datasets, demonstrating its effectiveness in automatically segmenting GBMs. The proposed method using prior knowledge in multimodal imaging can improve the contouring accuracy of GBMs, which holds the potential to improve the quality and efficiency of GBMs' radiotherapy.

Optimizing Decision Support Alerts to Reduce Telemetry Duration: A Multicenter Evaluation.

Telemetry monitoring is crucial for high-risk patients but excessive use beyond practice standards increases costs. Prior studies have shown that electronic health record (EHR) alerts reduce low-value telemetry monitoring. However, specific components of these alerts that contribute to effectiveness are unknown. We aimed to revise previously implemented EHR Best Practice Advisories (BPAs) to optimize their effectiveness in reducing telemetry duration. The secondary objective was to assess the impact on clinicians' alert burden. A multicenter retrospective study was conducted at Johns Hopkins Hospital (JHH), Johns Hopkins Bayview Medical Center (JHBMC), and Howard County General Hospital (HCGH). An EHR alert in the form of a BPA was previously implemented at JHH/JHBMC, firing at 24, 48, or 72 hours based on order indication. HCGH used an alert firing every 24 hours. A revised BPA was implemented at all hospitals optimizing the prior JHH/JHBMC alert by including patient-specific telemetry indications, restricting alerts to daytime hours (8:00 a.m.-6:00 p.m.), and embedding the discontinuation order within the BPA alert. A retrospective analysis from October 2018 to December 2021 was performed. The primary outcome was telemetry duration. The secondary outcome was the mean monthly BPA alerts per patient-day. Compared with the original BPA, the revised BPA reduced telemetry duration by a mean of 6.7 hours (95% CI: 5.2-9.1 hours, p < 0.001) at JHH/JHBMC, with a minimal increase of 0.06 mean monthly BPA alerts per patient-day (p < 0.001). The BPA acceptance rate increased from 7.8 to 31.3% postintervention at JHH/JHBMC (p < 0.0001). At HCGH, the intervention led to a mean monthly reduction of 20.2 hours in telemetry duration per hospitalization (95% CI: 19.1-22.8 hours, p < 0.0001). Optimizing EHR BPAs reduces unnecessary telemetry duration without substantially increasing clinician alert burden. This study highlights the importance of tailoring EHR alerts to enhance effectiveness and promote value-based care.

Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows.

Drug-resistant tuberculosis remains a major obstacle in ending the global tuberculosis epidemic. Deployment of molecular tools for comprehensive drug resistance profiling is imperative for successful detection and characterisation of tuberculosis drug resistance. We aimed to assess the diagnostic accuracy of a new class of molecular diagnostics for drug-resistant tuberculosis. We conducted a prospective, cross-sectional, multicentre clinical evaluation of the performance of two targeted next-generation sequencing (tNGS) assays for drug-resistant tuberculosis at reference laboratories in three countries (Georgia, India, and South Africa) to assess diagnostic accuracy and index test failure rates. Eligible participants were aged 18 years or older, with molecularly confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant tuberculosis. Sensitivity and specificity for both tNGS index tests (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT] Tuberculosis Drug Resistance Test) were calculated for rifampicin, isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide, bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against a composite reference standard of phenotypic drug susceptibility testing and whole-genome sequencing. Between April 1, 2021, and June 30, 2022, 832 individuals were invited to participate in the study, of whom 720 were included in the final analysis (212, 376, and 132 participants in Georgia, India, and South Africa, respectively). Of 720 clinical sediment samples evaluated, 658 (91%) and 684 (95%) produced complete or partial results on the GenoScreen and ONT tNGS workflows, respectively, with 593 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence data. Both workflows had sensitivities and specificities of more than 95% for rifampicin and isoniazid, and high accuracy for fluoroquinolones (sensitivity approximately ≥94%) and second line-injectables (sensitivity 80%) compared with the composite reference standard. Importantly, these assays also detected mutations associated with resistance to critical new and repurposed drugs (bedaquiline, linezolid) not currently detectable by any other WHO-recommended rapid diagnostics on the market. We note that the current format of assays have low sensitivity (≤50%) for linezolid and more work on mutations associated with drug resistance is needed. This multicentre evaluation demonstrates that culture-free tNGS can provide accurate sequencing results for detection and characterisation of drug resistance from Mycobacterium tuberculosis clinical sediment samples for timely, comprehensive profiling of drug-resistant tuberculosis. Unitaid.

A French multicenter analytical evaluation of the automated Lumipulse G sNfL blood assay (Fujirebio®) and its comparison to four other immunoassays for serum neurofilament light chain assessment in clinical settings

ObjectivesMeasurement of serum neurofilament light chain (sNfL) protein is becoming a key biomarker for many neurological diseases. Several immunoassays have been developed to meet these clinical needs, revealing significant differences in terms of variability and results. Here, we propose a French multicenter comparison of 5 sNfL assays. Methods6 replicates of 3 pools with low (10 pg/mL), medium (30 pg/mL) and high (100 pg/mL) sNfL values and one replicate of 12 samples with growing sNfL values were analyzed by six independent French clinical laboratories. The analytical performances of the sNfL blood assay (Fujirebio®) on Lumipulse G were first evaluated then compared to four other immunoassays: NF-light V2 (Quanterix®) on SiMOA HD-X, Human NF-L (Biotechne®) on Ella, R-Plex Human Neurofilament L (MSD®) on Sector 2400; manual ELISA test using Uman Diagnostic/Quanterix®. ResultsInter-center comparison of the Lumipulse blood assay revealed limited but significant differences in the mean sNfL values across low, medium, and high pools between each city (p < 0.001) and between the two different batches used. Coefficients of variation of pools ranged from 2.0 to 16.9 %. Z-score of sNfL results of the 12 samples ranged from −1.70 to +1.71. Inter-technique comparison showed a systematic difference of sNfL values, with a overestimation of MSD and Ella over other tests. Nonetheless, results were all significantly correlated (p < 0.001). ConclusionThe automated Lumipulse assay produced comparable sNfL values across laboratories; but further adjustments are needed to harmonize sNfL results. Biologists and physicians should be aware of the variability in results between different immunoassay suppliers.

Commentary on 'Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net)'.

Commentary on 'Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net)'.

Multicenter evaluation of CT deep radiomics model in predicting Leibovich score risk groups for non-metastatic clear cell renal cell carcinoma

BackgroundNon-metastatic clear cell renal cell carcinoma (nccRCC) poses a significant risk of postoperative recurrence and metastasis, underscoring the importance of accurate preoperative risk assessment. While the Leibovich score is effective, it relies on postoperative histopathological data. This study aims to evaluate the efficacy of CT radiomics and deep learning models in predicting Leibovich score risk groups in nccRCC, and to explore the interrelationship between CT and pathological features. Patients and MethodsThis research analyzed 600 nccRCC patients from four datasets, dividing them into low (Leibovich scores of 0–2) and intermediate to high risk (Leibovichscores exceeding 3) groups. Radiological models were developed from CT subjective features, and radiomics and deep learning models were constructed from CT images. Additionally, a deep radiomics model and a fusion model integrating radiological, radiomics, and deep learning features were introduced. Model performance was assessed by AUC values, while survival differences across predicted groups were analyzed using survival curves and the DeLong test. Moreover, the research investigated the connection between CT and pathological features derived from whole-slide pathological images in the second validation dataset. ResultsWithin the training dataset, four radiological, three radiomics, and thirteen deep learning features were selected to develop models predicting nccRCC Leibovich score risk groups. The deep radiomics model demonstrated superior predictive accuracy, evidenced by AUC values of 0.881, 0.829, and 0.819 in external validation datasets. Notably, significant differences in overall survival were observed among patients classified by this model (DeLong test p < 0.05 across all datasets). Furthermore, a correlation and complementarity were observed between deep radiomics features and pathological deep learning features. ConclusionsThe CT deep radiomics model precisely predicts nccRCC Leibovich score risk groups preoperatively and highlights the synergistic effect between CT and pathological data.

A Multicenter Evaluation of Clopidogrel Resistance and Its Role in Predicting Stent Thrombosis in Transcarotid Artery Revascularization

OBJECTIVEClopidogrel resistance testing is not routine prior to Transcarotid Artery Revascularization (TCAR) and resistance rates are not well described in this setting, despite frequent use of periprocedural clopidogrel. We compared two resistance testing modalities to determine the relationship between resistance and stent outcomes. METHODSConsecutive patients undergoing TCAR at three institutions were retrospectively identified. Clopidogrel-resistance testing results and outcomes were described. RESULTSA total of 210 patients underwent TCAR from 2018-2022. 154 (73%) were on dual antiplatelet therapy (DAPT) for at least 7 days prior to TCAR. Twenty-nine patients were not on DAPT due to therapeutic anticoagulation and most (38/56, 68%) received a loading dose of a second antiplatelet the day of surgery. Twenty-five patients (11.9%) experienced stent thrombosis within 30 days. Patients not on DAPT for at least 7 days prior to surgery were more prone to stent thrombosis (16.7% vs 10.4%, p=.164). Over half (133/210, 63%) of patients underwent resistance testing, 25 with thromboelastogram with platelet mapping (TEG-PM), 103 with VerifyNow P2Y12 platelet reactivity assay, and 5 with both. Prevalence of Clopidogrel resistance among tested patients was 41%. In patients tested using both TEG-PM and VerifyNow, agreement was poor (Cohen’s Kappa -0.05). Among patients with resistance, 12 (22%) experienced stent thrombosis. Comparatively, 8 (10%) patients without resistance developed thrombosis (p=.021). VerifyNow P2Y12 platelet reactivity assay correctly predicted Clopidogrel-resistance more accurately than TEG-PM (70% versus 40%, p=.025) and had sensitivity of 56% and specificity of 73% for stent thrombosis. CONCLUSIONOur multi-institutional cohort confirms a high rate of Clopidogrel resistance in patients undergoing TCAR, with higher acute stent thrombosis rates noted in patients with resistance. VerifyNow P2Y12 platelet reactivity assays more reliably predict Clopidogrel resistance than TEG-PM.

Multicentre evaluation of in vitro activity of contezolid against drug-resistant Staphylococcus and Enterococcus.

To investigate susceptibility to contezolid, a novel oxazolidinone, multicentre surveillance was conducted involving 2449 strains of Staphylococcus and Enterococcus collected from 65 hospitals across China. The MICs of contezolid, linezolid and other clinically significant antibiotics were determined by the broth microdilution method. Consistency with the broth microdilution method for contezolid was assessed using agar dilution method, as well as disc diffusion and ETEST for linezolid, respectively. WGS was conducted on all 20 linezolid-resistant and 30 randomly non-resistant strains to analyse linezolid resistance genes (optrA, poxtA, cfr) and 23S rRNA mutation sites. All strains exhibited WT susceptibility to contezolid, while resistance proportions to daptomycin, vancomycin, teicoplanin, tigecycline and eravacycline ranged from 0% to 5.2% in Staphylococcus, and from 0% to 7.8% in Enterococcus. Linezolid resistance was higher in Enterococcus faecalis (4.4%) compared with Enterococcus faecium (0.2%). Contezolid showed a lower MIC50 (0.5 mg/L) than linezolid (2 mg/L) for methicillin-resistant Staphylococcus. Against Enterococcus, contezolid demonstrated a cumulative MIC percentage of 70% for VRE and 39.1% for E. faecalis (at MIC = 1 mg/L), whereas linezolid showed 0% and 1.1%, respectively. Among the 20 linezolid-resistant Enterococcus strains, all carried the optrA gene without 23S rRNA mutations. For contezolid, MICs were 4 mg/L for 19 strains and 2 mg/L for 1 strain. The ETEST, agar dilution and disc diffusion methods showed essential and categorical agreements of >90% for linezolid, with no major errors or very major errors. Contezolid demonstrated significant in vitro antibacterial activity against methicillin-resistant Staphylococcus, VRE and linezolid-resistant E. faecalis.

Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial

BackgroundThe rate of vitamin D deficiency (VDD) in critically ill children worldwide has been estimated at 50%. These children are at risk of multiple organ dysfunction, chronic morbidity, and decreased health related quality of life (HRQL). Pediatric and adult ICU clinical trials suggest that VDD is associated with worse clinical outcomes, although data from supplementation trials are limited and inconclusive. Our group’s phase II multicenter dose evaluation pilot study established the efficacy and safety of an enteral weight-based cholecalciferol loading dose to rapidly restore vitamin D levels in critically ill children.MethodsOur aim is to evaluate the impact of this dosing regimen on clinical outcomes. VITdALIZE-KIDS is a pragmatic, phase III, multicenter, double-blind RCT aiming to randomize 766 critically ill children from Canadian PICUs. Participants are randomized using a 1:1 scheme to receive a single dose at enrollment of enteral cholecalciferol (10,000 IU/kg, max 400,000 IU) or placebo. Eligibility criteria include critically ill children aged newborn (> 37 weeks corrected gestational age) to < 18 years who have blood total 25-hydroxyvitamin D < 50 nmol/L. The primary objective is to determine if rapid normalization of vitamin D status improves HRQL at 28 days following enrollment. The secondary objective is to evaluate the impact of rapid normalization of vitamin D status on multiple organ dysfunction. The study includes additional tertiary outcomes including functional status, HRQL and mortality at hospital discharge and 90 days, PICU and hospital length of stay, and adverse events related to vitamin D toxicity. Additionally, we are performing comprehensive vitamin D speciation and non-targeted metabolite profiling as part of a sub-study for the first 100 participants from whom an enrollment and at least one post-intervention blood and urine sample were obtained.DiscussionThe VITdALIZE-KIDS trial is the first phase III, multicenter trial to evaluate whether rapid normalization of vitamin D status could represent a simple, inexpensive, and safe means of improving outcomes following pediatric critical illness. Recruitment was initiated in June 2019 and is expected to continue to March 2026.Trial registrationClinicaltrials.gov, NCT03742505. Study first submitted on November 12, 2018 https://clinicaltrials.gov/study/NCT03742505

Multi-center evaluation of 19 loci hybrid capture NGS assay on illumina instruments

Multi-center evaluation of 19 loci hybrid capture NGS assay on illumina instruments

Determining the Association of Hyperoxia While on Extracorporeal Life Support with Mortality in Neonates Following Norwood Operation

Background: Patients requiring extracorporeal life support (ECLS) support post-Norwood operation constitute an extremely high-risk group. Materials &amp; Methods: We retrospectively aimed to evaluate the relationship of hyperoxia with mortality and other clinical outcomes in patients who required ECLS following Norwood operation between January/2010 – December/2020 in a large volume center. Results: During the study period 65 patients required ECLS post-Norwood. Using receiver operating characteristic (ROC) curve analysis, mean PaO2 of 182 mmHg in the first 48-hours on ECLS was determined to have the optimal discriminatory ability for mortality (sensitivity 68%, specificity 70%). Of the 65 patients, 52% had PaO2&gt;182 mmHg and were designated as hyperoxia-group. Patients in the hyperoxia-group had longer cardiopulmonary bypass time (187 vs 165 minutes, p=0.023), shorter duration from CICU arrival to ECLS-cannulation (13.28 vs 132.58 hours, p=0.003), higher serum lactate within 2-hours from ECLS-canulation (14.55 vs 5.80, p=0.01), higher ECLS flows in the 1st 4-hours (152.68 vs 124.14, p=0.006), and higher mortality (77% vs 39%, p=0.005). In the unadjusted-analysis, using a derived cut-point, patients in the hyperoxia-group had 5.15-higher odds of mortality (p=0.003). However, this association was insignificant when adjusting for confounding variables (p=0.104). Using functional status scale, new morbidity (38% vs 21%), and unfavorable outcomes (13% vs 5%) were higher in the hyperoxia-group. Despite being higher in the hyperoxia group, this did not reach statistical significance. Conclusion: Neonates with hyperoxia (PaO2 &gt;182 torr) during the first 48-hours of ECLS post-Norwood operation had 5-times higher odds of mortality in the unadjusted analysis, however, this was insignificant when adjusting for confounding variables. Patients in the hyperoxia-group had shorter duration from CICU arrival to ECLS-cannulation, higher serum lactate prior to ECLS-canulation, and higher ECLS flows in the 1st 4-hours, (p&lt;0.05). Multicenter evaluation of this modifiable risk-factor is imperative to improve the care of this high-risk cohort.