Citations

Background Physiological monitoring systems, like Masimo, used during inpatient hospitalisation, offer a non-invasive approach to capture critical vital signs data. These systems trigger alarms when measurements deviate from preset parameters. However, often non-urgent or potentially false alarms contribute to ‘alarm fatigue,’ a form of sensory overload that can have adverse effects on both patients and healthcare staff. The Joint Commission, in 2021, announced a target to mitigate alarm fatigue-related fatalities through improved alarm management. Yet, no established guidelines are presently available. This study aims to address alarm fatigue at the Mayo Clinic to safeguard patient safety, curb staff burnout and improve the sensitivity of oxygen saturation monitoring to promptly detect emergencies. Methods A quality improvement project was conducted to combat minimise the false alarm burden, with data collected 2 months prior to intervention commencement. The project’s goal was to decrease the total alarm value by 20% from 55%–85% to 35%–75% within 2 months, leveraging quality improvement methodologies. Interventions February to April 2021, we implemented a two-pronged intervention: (1) instituting a protocol to evaluate patients’ continuous monitoring needs and discontinuing it when appropriate, and (2) introducing educational signage for patients and Mayo Clinic staff on monitoring best practices. Results Baseline averages of red alarms (158.6), manual snoozes (37.8) and self-resolves (120.7); the first postintervention phase showed reductions in red alarms (125.5), manual snoozes (17.8) and self-resolves (107.8). Second postintervention phase recorded 138 red alarms, 13 manual snoozes and 125 self-resolves. Baseline comparison demonstrated an average of 16.92% reduction of alarms among both interventions (p value: 0.25). Conclusion Simple interventions like education and communication techniques proved instrumental in lessening the alarm burden for patients and staff. The findings underscore the practical use and efficacy of these methods in any healthcare setting, thus contributing to mitigating the prevalent issue of alarm fatigue.

2017 Background: Response Assessment in Neuro-Oncology (RANO) criteria for high-grade and low-grade glioma (HGG and LGG) were developed to improve reliability of response assessment in glioma trials. Several limitations of the original RANO criteria have been reported. Methods: To address limitations of the original RANO criteria, a large cohort of patients with newly diagnosed and recurrent glioblastoma were evaluated comparing RANO-HGG with modified RANO (mRANO) and immunotherapy RANO (iRANO) criteria to inform the following proposed updates (RANO 2.0). Results: Based on the 2021 WHO classification of glioma, we recommend a single common set of criteria for all gliomas regardless of WHO grade and IDH mutational status. These criteria will be used for all trials regardless of the treatment modalities being evaluated. In newly diagnosed glioblastoma, the post-radiotherapy MRI, usually obtained approximately 4 weeks after completion of radiotherapy, rather than the post-surgical MRI as proposed in original RANO criteria, will be used as the baseline for comparison of subsequent scans. Since the incidence of pseudoprogression is high in the first 3 months following radiotherapy, confirmation of progression during this period with a repeat MRI (in 4-8 weeks) will be required for determining radiographic progression of disease (PD) if the patient is clinically stable. However, confirmation scans are not mandatory after this period nor for recurrent tumors since these scans do not appear to improve reliability in determining progression. For agents with a high likelihood of producing pseudoprogression such as viral therapies and some other immunotherapies, mandatory confirmation of progression with a repeat MRI is an option. The primary measurement will remain the 2-dimensional maximum cross-sectional area of tumor as the simplest method, but where resources are available, volumetric measurements are an option. For IDH wild-type tumors with contrast enhancement, non-enhancing tumor will no longer be evaluated with the possible exception of patients receiving antiangiogenic therapies. However, in tumors with a significant non-enhancing component, both the contrast enhancing and non-enhancing components will be evaluated as target lesions. Conclusions: We hope that these and other proposed changes by the RANO working group will improve response assessment in glioma clinical trials and help the development of more effective therapy for patients.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE–APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Abstract Durable objective response rate (ORR) remains a meaningful endpoint in recurrent cancer; however, the target ORR for single-arm recurrent glioblastoma trials has not been based on historic information or tied to patient outcomes. The current study reviewed 68 treatment arms comprising 4793 patients in past trials in recurrent glioblastoma in order to judiciously define target ORRs for use in recurrent glioblastoma trials. ORR was estimated at 6.1% [95% CI 4.23; 8.76%] for cytotoxic chemothera + pies (ORR = 7.59% for lomustine, 7.57% for temozolomide, 0.64% for irinotecan, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for (select) immunotherapies, and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2= 0.4078, P < .0001), biologics (R2= 0.4003, P = .0003), and immunotherapy trials (R2= 0.8994, P < .0001), but not anti-angiogenic agents (R2= 0, P = .8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2= 0.3900, P < .0001; mOS [weeks] = 1.4xORR + 24.8). Assuming an ineffective cytotoxic (control) therapy has ORR = 7.6%, the average ORR for lomustine and temozolomide trials, a sample size of ≥40 patients with target ORR>25% is needed to demonstrate statistical significance compared to control with a high level of confidence (P < .01) and adequate power (>80%). Given this historic data and potential biases in patient selection, we recommend that well-controlled, single-arm phase II studies in recurrent glioblastoma should have a target ORR >25% (which translates to a median OS of approximately 15 months) and a sample size of ≥40 patients, in order to convincingly demonstrate antitumor activity. Crucially, this response needs to have sufficient durability, which was not addressed in the current study.

Abstract Eosinophilia is a common sequela of treatment in patients infected with the parasitic helminth Wuchereria bancrofti. We investigated the relationship between peripheral blood eosinophil levels and serum levels of eosinophil granule major basic protein (MBP) and Charcot-Leyden crystal (CLC) protein in 37 patients with Bancroft’s filariasis who were treated with diethylcarbamazine (DEC). Before treatment with DEC, eosinophil levels and serum levels of CLC protein, but not MBP, were found to be significantly elevated in both filariasis patients and an uninfected endemic control population. After treatment, patients with microfilaremia developed an initial eosinopenia followed by significant increases in their eosinophil levels and serum levels of both MBP and CLC protein, which peaked 1 to 2 wk after initiating treatment. Before treatment, eosinophil levels and serum levels of MBP and CLC protein were unrelated to the number of microfilariae in circulation, but after treatment, the degree of eosinophilia and the elevations in serum MBP and CLC protein were significantly correlated with the patients’ microfilarial worm burdens before treatment. In microfilaremic patients on DEC therapy, there was a statistically significant increase in serum MBP levels concomitant with the initial decrease in eosinophil levels observed on day 1 of therapy in these patients. Patients with filariasis (elephantiasis, hydrocoeles, or filarial fevers) but without microfilaremia, as well as an uninfected endemic control population, showed no change in their eosinophil levels or serum MBP or CLC protein levels during an identical course of DEC therapy. The eosinophilic response resulting from DEC therapy of patients with microfilaremia provides a unique opportunity to study the relationship between eosinophilia, eosinophil function, and possibly eosinophilopoiesis as reflected by the synthesis and/or release of eosinophil proteins in humans exposed to a quantifiable antigenic stimulus.

Abstract Durable overall response rate (ORR) remains a meaningful endpoint in recurrent GBM; however, the target ORR for single arm recurrent GBM trials has not been based on historic information or tied to patient outcomes. The current study reviewed past trials in recurrent GBM in order to judiciously define target ORRs for use in recurrent GBM trials. After reviewing 69 treatment arms comprising 4,971 patients, ORR was 6.1%[95% CI 4.23; 8.76%] for cytotoxic chemotherapies (ORR=7.59% for CCNU, 7.57% for TMZ, 0.64% for CPT-11, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for immunotherapies (select trials), and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2=0.4078, P< 0.0001), biologics (R2=0.4003, P=0.0003), and immunotherapy trials (R2=0.8994, P< 0.0001), but not anti-angiogenic agents (R2=0, P=0.8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2=0.3164, P< 0.0001; mOS[weeks]=0.6xORR+28.9), suggesting an ORR >20% results in an mOS of > 40.9 weeks, which is double the survival estimate of a treatment with ORR=0% and ≥ 2 months longer than treatments with ORR=5%. Assuming an ineffective therapy (control) has ORR=5%, a trial of 32 patients with a target ORR=20% leads to the 95% confidence interval higher than the control group. We conclude that single arm phase II studies in recurrent GBM with ≥ 32 patients should have a target ORR ≥ 20%. This was associated with a median OS of approximately 1 year. Importantly, durability of response should also be considered and was not assessed in the current meta-analysis.

Abstract Isocitrate dehydrogenase (IDH) mutant gliomas are the most common adult, malignant primary brain tumors diagnosed in patients younger than 50, constituting an important cause of morbidity and mortality. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors, sparking multiple efforts to improve their diagnosis and treatment. In this consensus review from the Society for Neuro-Oncology (SNO), the current diagnosis and management of IDH-mutant gliomas will be discussed. In addition, novel therapies, such as targeted molecular therapies and immunotherapies, will be reviewed. Current challenges and future directions for research will be discussed.

AbstractBackgroundBiomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil‐derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil‐associated diseases treated with mepolizumab, benralizumab, or dexpramipexole.MethodsEosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay.ResultsUrine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups.ConclusionsMeasurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

Abstract Background Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. Methods In a multicenter, case-control, public health investigation of children ages 5–18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. Results We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR [aOR]: .16; 95% CI: .10–.26), including among children ages 5–11 years (aOR: .22; 95% CI: .10–.52), ages 12–18 years (aOR: .10; 95% CI: .05–.19), and during the Delta (aOR: .06; 95% CI: .02–.15) and Omicron (aOR: .22; 95% CI: .11–.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03–.22) in 12–18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated. Conclusions Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5–18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.