Evaluation of the Parkinson's Remote Interactive Monitoring System in a Clinical Setting: Usability Study.

BACKGROUND: The fastest-growing neurological disorder is Parkinson disease (PD), a progressive neurodegenerative disease that affects 10 million people worldwide. PD is typically treated with levodopa, an oral pill taken to increase dopamine levels, and other dopaminergic agonists. As the disease advances, the efficacy of the drug diminishes, necessitating adjustments in treatment dosage according to the patient's symptoms and disease progression. Therefore, remote monitoring systems that can provide more detailed and accurate information on a patient's condition regularly are a valuable tool for clinicians and patients to manage their medication. The Parkinson's Remote Interactive Monitoring System (PRIMS), developed by PragmaClin Research Inc, was designed on the premise that it will be an easy-to-use digital system that can accurately capture motor and nonmotor symptoms of PD remotely. OBJECTIVE: We performed a usability evaluation in a simulated clinical environment to assess the ease of use of the PRIMS and determine whether the product offers suitable functionality for users in a clinical setting. METHODS: Participants were recruited from a user sign-up web-based database owned by PragmaClin Research Inc. A total of 11 participants were included in the study based on the following criteria: (1) being diagnosed with PD and (2) not being diagnosed with dementia or any other comorbidities that would make it difficult to complete the PRIMS assessment safely and independently. Patient users completed a questionnaire that is based on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale. Interviews and field notes were analyzed for underlying themes and topics. RESULTS: In total, 11 people with PD participated in the study (female individuals: n=5, 45%; male individuals: n=6, 55%; age: mean 66.7, SD 7.77 years). Thematic analysis of the observer's notes revealed 6 central usability issues associated with the PRIMS. These were the following: (1) the automated voice prompts are confusing, (2) the small camera is problematic, (3) the motor test exhibits excessive sensitivity to the participant's orientation and position in relation to the cameras, (4) the system poses mobility challenges, (5) navigating the system is difficult, and (6) the motor test exhibits inconsistencies and technical issues. Thematic analysis of qualitative interview responses revealed four central themes associated with participants' perspectives and opinions on the PRIMS, which were (1) admiration of purpose, (2) excessive system sensitivity, (3) video instructions preferred, and (4) written instructions disliked. The average system usability score was calculated to be 69.2 (SD 4.92), which failed to meet the acceptable system usability score of 70. CONCLUSIONS: Although multiple areas of improvement were identified, most of the participants showed an affinity for the overarching objective of the PRIMS. This feedback is being used to upgrade the current PRIMS so that it aligns more with patients' needs.

Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

This is a summary of the original article ?Overall survival with osimertinib in resected EGFR-mutated NSCLC.Ë® Osimertinib blocks the activity of the epidermal growth factor receptor (EGFR) on cancer cells, causing cancer cell death and tumor shrinkage, and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The ADAURA study assessed the effects of osimertinib versus placebo in patients with EGFR-mutated (exon 19 deletion or L858R) early stage (IB-IIIA) NSCLC removed by surgery (resected). Previous results from ADAURA demonstrated that patients treated with osimertinib stayed alive and cancer-free (disease-free survival) significantly longer than patients who received placebo. Recent data showed the overall length of time patients were alive after starting treatment (overall survival). In both the primary stage II-IIIA and overall stage IB-IIIA populations, patients in the osimertinib group had a significant 51% reduction in the risk of death compared with the placebo group. The data demonstrated that osimertinib after surgery significantly improved overall survival in patients with resected, EGFR-mutated, stage IB-IIIA NSCLC.

Expanding access to magnetic resonance education through open-source web tutorials.

This study presents a tool that introduces the fundamental concepts of magnetic resonance (MR) by integrating related science, technology, engineering, arts, and mathematical (STEAM) topics in the form of games to improve the access to MR education.

Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial.

BACKGROUND: In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy. METHODS: Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing EGFR/ALK alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population). Assessments included OS, progression-free survival, and objective response rate. Exploratory analyses included efficacy by tumor PD-L1 expression and histology and in patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events (TRAEs), and a treatment-switching adjustment analysis using inverse probability of censoring weighting. RESULTS: With a 47.9-month minimum follow-up for OS, nivolumab plus ipilimumab with chemotherapy continued to prolong OS over chemotherapy in all randomized patients (HR 0.74, 95% CI 0.63 to 0.87; 4-year OS rate: 21% versus 16%), regardless of tumor PD-L1 expression (HR (95% CI): PD-L1<1%, 0.66 (0.50 to 0.86) and ≥1%, 0.74 (0.60 to 0.92)) or histology (squamous, 0.64 (0.48 to 0.84) and non-squamous, 0.80 (0.66 to 0.97)). In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy due to TRAEs (n=61), the 4-year OS rate was 41%. With treatment-switching adjustment for the 36% of patients receiving subsequent immunotherapy in the chemotherapy arm, the estimated HR of nivolumab plus ipilimumab with chemotherapy versus chemotherapy was 0.66 (95% CI 0.55 to 0.80). No new safety signals were observed. CONCLUSIONS: In this 4-year update, patients treated with nivolumab plus ipilimumab with chemotherapy continued to have long-term, durable efficacy benefit over chemotherapy regardless of tumor PD-L1 expression and/or histology. A greater estimated relative OS benefit was observed after adjustment for subsequent immunotherapy use in the chemotherapy arm. These results further support nivolumab plus ipilimumab with chemotherapy as a first-line treatment for patients with metastatic/recurrent NSCLC, including those with tumor PD-L1<1% or squamous histology, populations with high unmet needs.

The Gárdos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells.

The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. In addition to this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties. Both the Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single-digit range, can be detected through transcriptome analysis of reticulocytes. Proteomics analysis of reticulocytes and mature RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch clamp method. While for the Gárdos channel, the activity in terms of ion currents is higher in reticulocytes compared to mature RBCs, for Piezo1, the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs. We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.

Lurbinectedin in small cell lung cancer: real-world experience of a multicentre national early access programme.

BACKGROUND AND AIMS: Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum-containing therapy. METHODS: Multicentre real-world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). RESULTS: Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second- (83%, 38/46) or subsequent- (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high-grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six-month OS was 44% (95% confidence interval (CI): 29.0-57.1). Twelve-month OS was 15% (95% CI: 6.5-26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8-2.9) and OS was 4.5 months (95% CI: 3.5-7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0-17.2). Individuals with a longer chemotherapy-free interval prior to lurbinectedin had longer PFS and OS. CONCLUSION: This real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials.

A Phase II trial of alternating osimertinib and gefitinib therapy in advanced EGFR-T790M positive non-small cell lung cancer: OSCILLATE.

In this phase II, single arm trial (ACTRN12617000720314), we investigate if alternating osimertinib and gefitinib would delay the development of resistance to osimertinib in advanced, non-small cell lung cancer (NSCLC) with the epidermal growth factor receptor (EGFR) T790M mutation (n = 47) by modulating selective pressure on resistant clones. The primary endpoint is progression free-survival (PFS) rate at 12 months, and secondary endpoints include: feasibility of alternating therapy, overall response rate (ORR), overall survival (OS), and safety. The 12-month PFS rate is 38% (95% CI 27.5-55), not meeting the pre-specified primary endpoint. Serial circulating tumor DNA (ctDNA) analysis reveals decrease and clearance of the original activating EGFR and EGFR-T790M mutations which are prognostic of clinical outcomes. In 73% of participants, loss of T790M ctDNA is observed at progression and no participants have evidence of the EGFR C797S resistance mutation following the alternating regimen. These findings highlight the challenges of treatment strategies designed to modulate clonal evolution and the clinical importance of resistance mechanisms beyond suppression of selected genetic mutations in driving therapeutic escape to highly potent targeted therapies.

Natural evolution of idiopathic carpal tunnel syndrome with respect to wrist and hand anthropometry: A prospective cohort study.

OBJECTIVE: A greater wrist depth/width ratio and wrist depth/palm length ratio are known risk factors for carpal tunnel syndrome. We hypothesized that these parameters might also predict progression in patients who were not surgically treated. METHODS: Seventy-eight patients with moderately severe idiopathic carpal tunnel syndrome of at least 10 months duration at recruitment, who declined surgical treatment and steroid injection, underwent repeated neurophysiological assessments after 3 years. A > 10% increase in median SNAP latency was taken as evidence of significant deterioration. RESULTS: Patients with a wrist ratio ≥ 0.72 showed a statistically significant deterioration in SNAP latency from 5.46 (SD 2.09) to 7.16 (SD 1.56) ms and in SNAP amplitude from 30.19 (SD 13.8) to 16.62 (SD 14.42) µv. For those with a wrist-to-palm ratio ≥ 0.42, SNAP latency deteriorated from 5.27 (SD 1.21) to 7.1 (SD 1.52) ms, and amplitude from 32.78 (SD 13.76) to 19.45 (SD 16.62) µv. Patients with lower ratios did not show significant changes in any neurophysiological parameter. The relative risk of significant deterioration in SNAP latency in patients with a wrist ratio ≥ 0.72 was 2.04 (95% CI 1.27-3.27). CONCLUSION: In untreated idiopathic carpal tunnel syndrome, patients with larger wrist and wrist-to-palm ratios are more likely to show neurophysiological progression.

Cord Blood Cortisol Level - A Possible Predictor for Respiratory Distress Syndrome in Preterm Neonates.

BACKGROUND: Respiratory Distress Syndrome (RDS) is a leading cause of death in premature infants. There are different clinical/ biochemical markers associated with the RDS. One of the potential biochemical markers is cortisol in cord blood. PURPOSE: This study aims to correlate cortisol levels in preterm neonates with RDS and to establish whether cord blood cortisol is a reliable predictor for RDS. MATERIALS AND METHODS: This prospective analytical study was conducted in a tertiary care hospital over nine months among fifty preterm neonates. Data were collected using proforma, and cord blood was collected at the time of delivery. Cortisol levels were compared and correlated to the development of RDS. RESULTS AND DISCUSSION: The mean ± SD cord blood cortisol level among preterm neonates was 5.97 ± 2.74 (SD) µg/dl. The levels were higher in neonates whose mothers received antenatal steroids and were significantly lower (2.86 ± 1.66 µg/dl) in those who developed RDS. Association between cord blood cortisol level and RDS was found with an odds ratio of 57.4, which was statistically significant. The percentage of babies developing RDS in mothers not covered with antenatal steroids was significantly higher than those covered (p-value is 0.000). The mean cord blood cortisol levels were exceptionally low (1.89 µg/dl) in neonates who expired compared to those who survived (7.02 µg/dl). CONCLUSION: There is an association between cord blood cortisol levels and RDS. Hence, Cord blood cortisol levels may be used to predict RDS and help initiate early treatment, thus preventing mortality and morbidity.

Incidence and determinants of perinatal mortality in five urban hospitals in Dar es Salaam, Tanzania: a cohort study with an embedded case-control analysis.

INTRODUCTION: Tanzania has one of the highest burdens of perinatal mortality, with a higher risk among urban versus rural women. To understand the characteristics of perinatal mortality in urban health facilities, study objectives were: I. To assess the incidence of perinatal deaths in public health facilities in Dar es Salaam and classify these into a) pre-facility stillbirths (absence of fetal heart tones on admission to the study health facilities) and b) intra-facility perinatal deaths before discharge; and II. To identify determinants of perinatal deaths by comparing each of the two groups of perinatal deaths with healthy newborns. METHODS: This was a retrospective cohort study among women who gave birth in five urban, public health facilities in Dar es Salaam. I. Incidence of perinatal death in the year 2020 was calculated based on routinely collected health facility records and the Perinatal Problem Identification Database. II. An embedded case-control study was conducted within a sub-population of singletons with birthweight ≥ 2000 g (excluding newborns with congenital malformations); pre-facility stillbirths and intra-facility perinatal deaths were compared with 'healthy newborns' (Apgar score ≥ 8 at one and ≥ 9 at five minutes and discharged home alive). Descriptive and logistic regression analyses were performed to explore the determinants of deaths. RESULTS: A total of 37,787 births were recorded in 2020. The pre-discharge perinatal death rate was 38.3 per 1,000 total births: a stillbirth rate of 27.7 per 1,000 total births and an intra-facility neonatal death rate of 10.9 per 1,000 live births. Pre-facility stillbirths accounted for 88.4% of the stillbirths. The case-control study included 2,224 women (452 pre-facility stillbirths; 287 intra-facility perinatal deaths and 1,485 controls), 99% of whom attended antenatal clinic (75% with more than three visits). Pre-facility stillbirths were associated with low birth weight (cOR 4.40; (95% CI: 3.13-6.18) and with maternal hypertension (cOR 4.72; 95% CI: 3.30-6.76). Intra-facility perinatal deaths were associated with breech presentation (aOR 40.3; 95% CI: 8.75-185.61), complications in the second stage (aOR 20.04; 95% CI: 12.02-33.41), low birth weight (aOR 5.57; 95% CI: 2.62-11.84), cervical dilation crossing the partograph's action line (aOR 4.16; 95% CI:2.29-7.56), and hypertension during intrapartum care (aOR 2.9; 95% CI 1.03-8.14), among other factors.  CONCLUSION: The perinatal death rate in the five urban hospitals was linked to gaps in the quality of antenatal and intrapartum care, in the study health facilities and in lower-level referral clinics. Urgent action is required to implement context-specific interventions and conduct implementation research to strengthen the urban referral system across the entire continuum of care from pregnancy onset to postpartum. The role of hypertensive disorders in pregnancy as a crucial determinant of perinatal deaths emphasizes the complexities of maternal-perinatal health within urban settings.

A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients.

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.

Updated efficacy and safety of entrectinib in NTRK fusion-positive non-small cell lung cancer.

OBJECTIVES: NTRK fusions result in constitutively active oncogenic TRK proteins responsible for âˆ¼ 0.2 % of non-small cell lung cancer (NSCLC) cases. Approximately 40 % of patients with advanced NSCLC develop CNS metastases; therefore, treatments with intracranial (IC) efficacy are needed. In an integrated analysis of three phase I/II studies (ALKA-372-001: EudraCT 2012-000148-88; STARTRK-1: NCT02097810; STARTRK-2: NCT02568267), entrectinib, a potent, CNS-active, TRK inhibitor, demonstrated efficacy in patients with NTRK fusion-positive (fp) NSCLC (objective response rate [ORR]: 64.5 %; 2 August 2021 data cut-off). We present updated data for this cohort. MATERIALS AND METHODS: Eligible patients were ≥ 18 years with locally advanced/metastatic, NTRK-fp NSCLC with ≥ 12 months of follow-up. Tumor responses were assessed by blinded independent central review (BICR) per RECIST v1.1 at Week 4 and every eight weeks thereafter. Co-primary endpoints: ORR; duration of response (DoR). Secondary endpoints included progression-free survival (PFS); overall survival (OS); IC efficacy; safety. Enrolment cut-off: 2 July 2021; data cut-off: 2 August 2022. RESULTS: The efficacy-evaluable population included 51 patients with NTRK-fp NSCLC. Median age was 60.0 years (range 22-88); 20 patients (39.2 %) had investigator-assessed baseline CNS metastases. Median survival follow-up was 26.3 months (95 % CI 21.0-34.1). ORR was 62.7 % (95 % CI 48.1-75.9), with six complete and 26 partial responses. Median DoR and PFS were 27.3 months (95 % CI 19.9-30.9) and 28.0 months (95 % CI 15.7-30.4), respectively. Median OS was 41.5 months. In patients with BICR-assessed baseline CNS metastases, IC-ORR was 64.3 % (n = 9/14; 95 % CI 35.1-87.2), including seven complete responders, and IC-DoR was 55.7 months. In the safety-evaluable population (n = 55), most treatment-related adverse events were grade 1/2; no treatment-related deaths were reported. CONCLUSION: Entrectinib has continued to demonstrate deep and durable systemic and IC responses in patients with NTRK-fp NSCLC.

Risk factors and treatment interventions associated with incomplete thrombus resolution and pulmonary hypertension after pulmonary embolism.

BACKGROUND: Residual pulmonary vascular occlusion (RPVO) affects one half of patients after a pulmonary embolism (PE). The relationship between the risk factors and therapeutic interventions for the development of RPVO and chronic thromboembolic pulmonary hypertension is unknown. METHODS: This retrospective review included PE patients within a 26-month period who had baseline and follow-up imaging studies (ie, computed tomography [CT], ventilation/perfusion scans, transthoracic echocardiography) available. We collected the incidence of RPVO, percentage of pulmonary artery occlusion (%PAO), baseline CT %PAO, most recent CT %PAO, and difference between the baseline and most recent %PAO on CT (Δ%PAO). RESULTS: A total of 354 patients had imaging reports available; 197 with CT and 315 with transthoracic echocardiography. The median follow-up time was 144 days (interquartile range [IQR], 102-186 days). RPVO was present in 38.9% of the 354 patients. The median Δ%PAO was -10.0% (IQR, -32% to -1.2%). Fewer patients with a provoked PE developed RPVO (P ≤ .01), and the initial troponin level was lower in patients who developed RPVO (P = .03). The initial thrombus was larger in the patients who received advanced intervention vs anticoagulation (baseline CT %PAO: median, 61.2%; [IQR, 27.5%-75.0%] vs median, 12.5% [IQR, 2.5%-40.0%]; P ≤ .0001). Catheter-directed thrombolysis (CDT; median Δ%PAO, -47.5%; IQR, -63.7% to -8.7%) and surgical pulmonary embolectomy (SPE; median Δ%PAO, -42.5; IQR, -68.1% to -18.7%) had the largest thrombus reduction compared with anticoagulation (P = .01). Of the 354 patients, 76 developed pulmonary hypertension; however, only 14 received pulmonary hypertension medications and 12 underwent pulmonary thromboendarterectomy. Cancer (odds ratio [OR], 1.7) and planned prolonged anticoagulation (>1 year; OR, 2.20) increased the risk of RPVO. In contrast, the risk was lower for men (OR, 0.61), patients with recent surgery (OR, 0.33), and patients treated with SPE (OR, 0.42). A larger Δ%PAO was found in men (coefficient, -8.94), patients with a lower body mass index (coefficient, -0.66), patients treated with CDT (coefficient, -18.12), and patients treated with SPE (coefficient, -21.69). A lower Δ%PAO was found in African-American patients (coefficient, 7.31). CONCLUSIONS: The use of CDT and SPE showed long-term benefit in thrombus reduction.

Brief Report: Real-World Toxicity and Survival of Combination Immunotherapy in Pleural Mesothelioma-RIOMeso.

BACKGROUND: Australia has one of the highest rates of asbestos-associated diseases. Mesothelioma remains an area of unmet need with a 5-year overall survival of 10%. First-line immunotherapy with ipilimumab and nivolumab is now a standard of care for unresectable pleural mesothelioma following the CheckMate 743 trial, with supportive data from the later line single-arm MAPS2 trial. RIOMeso evaluates survival and toxicity of this regimen in real-world practice. METHODS: Demographic and clinicopathologic data of Australian patients treated with ipilimumab and nivolumab in first- and subsequent-line settings for pleural mesothelioma were collected retrospectively. Survival was reported using the Kaplan-Meier method and compared between subgroups with the log-rank test. Toxicity was investigator assessed using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 119 patients were identified from 11 centers. The median age was 72 years, 83% were male, 92% had Eastern Cooperative Oncology Group less than or equal to 1, 50% were past or current smokers, and 78% had known asbestos exposure. In addition, 50% were epithelioid, 19% sarcomatoid, 14% biphasic, and 17% unavailable. Ipilimumab and nivolumab were used first line in 75% of patients. Median overall survival (mOS) was 14.5 months (95% confidence interval [CI]: 13.0-not reached [NR]) for the entire cohort. For patients treated first line, mOS was 14.5 months (95% CI: 12.5-NR) and in second- or later-line patients was 15.4 months (95% CI: 11.2-NR). There was no statistically significant difference in mOS for epithelioid patients compared with nonepithelioid (19.1 mo [95% CI: 15.4-NR] versus 13.0 mo [95% CI: 9.7-NR], respectively, p = 0.064). Furthermore, 24% of the patients had a Common Terminology Criteria for Adverse Events grade greater than or equal to 3 adverse events, including three treatment-related deaths. Colitis was the most frequent adverse event. CONCLUSIONS: Combination immunotherapy in real-world practice has poorer survival outcomes and seems more toxic compared with clinical trial data. This is the first detailed report of real-world survival and toxicity outcomes using ipilimumab and nivolumab treatment of pleural mesothelioma.

Development and validation of a stressor-coping style scale for students in a public medical school

Background@#The medical curriculum is one of the most stressful academic curricula worldwide. Studies indicate that great levels of stress, that encompass academics to personal life, may be connected to a number of worrying statistics for the mental health of Philippine medical students.@*Objectives@#To develop a validated stressor-coping style scale for students in a public medical school.@*Methods@#The study employed a sequential mixed-methods design. An open-ended questionnaire was used to determine the common stressors and coping styles through convenience sampling. A scale was constructed from this data and was statistically tested for concurrent validity and reliability from a random sample.@*Results@#Following thematic analysis, an initial six stressor domains and eleven coping mechanisms were identified. However, after item analysis and principal component analysis of responses, the scale was transformed to seven stressor domains and five coping mechanism domains. All of which are deemed internally consistent (α>0.6). Scores from the scale were also convergent with the scores of Brief COPE (r=0.5 to 0.9). @*Conclusions@#The developed stressor-coping style scale for medical students is a reliable and valid tool for Filipino medical students in a public medical school.

Early stage of erythrocyte sedimentation rate test: Fracture of a high-volume-fraction gel.

Erythrocyte sedimentation rate (ESR) is a clinical parameter used as a nonspecific marker for inflammation, and recent studies have shown that it is linked to the collapse of the gel formed by red blood cells (RBCs) at physiological hematocrits (i.e. RBC volume fraction). Previous research has suggested that the observation of a slower initial dynamics is related to the formation of fractures in the gel. Moreover, RBC gels present specific properties due to the anisotropic shape and flexibility of the RBCs. Namely, the onset of the collapse is reached earlier and the settling velocity of the gel increases with increasing attraction between the RBCs, while the gel of spherical particles shows the opposite trend. Here, we report experimental observations of the gel structure during the onset of the collapse. We suggest an equation modeling this initial process as fracturing of the gel. We demonstrate that this equation provides a model for the motion of the interface between blood plasma and the RBC gel, along the whole time span. We also observe that the increase in the attraction between the RBCs modifies the density of fractures in the gel, which explains why the gel displays an earlier onset when the aggregation energy between the RBCs increases. Our work uncovers the detailed physical mechanism underlying the ESR and provides insights into the fracture dynamics of an RBC gel. These results can improve the accuracy of clinical measurements.

Evaluating the effects of the color wheel system on a teacher's repeated directions.

Students are less likely to hear and understand teacher-delivered directions or instructions when they are attending to other activities (e.g., a classmate, a previously assigned task). A classroom management system known as the Color Wheel System includes rules and transition procedures designed to increase the probability that students stop their current activities and attend to teachers as they deliver directions or instructions for the next activity. A withdrawal design was used to evaluate the effects of the Color Wheel System on a teacher's repeated directions in a first-grade general-education classroom. Results showed large and immediate decreases in teacher repeated directions both times the Color Wheel System was applied and an immediate increase when it was withdrawn. Discussion focuses on limitations and directions for future longitudinal research evaluating the effects of the Color Wheel System on uninterrupted teaching and learning time, classroom climates, student-teacher relationships, and compliance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effectiveness of a Novel Rapid Infusion Device and Clinician Education for Early Fluid Therapy by Emergency Medical Services in Sepsis Patients: A Pre-Post Observational Study.

OBJECTIVE: Emergency medical services (EMS) clinicians are tasked with early fluid resuscitation for patients with sepsis. Traditional methods for prehospital fluid delivery are limited in speed and ease-of-use. We conducted a comparative effectiveness study of a novel rapid infusion device for prehospital fluid delivery in suspected sepsis patients. METHODS: This pre-post observational study evaluated a hand-operated, rapid infusion device in a single large EMS system from July 2021-July 2022. Prior to device deployment, EMS clinicians completed didactic and simulation-based device training. Data were extracted from the EMS electronic health record. Eligible patients included adults with suspected sepsis treated by EMS with intravenous fluids. The primary outcome was the proportion of patients receiving goal fluid volume (at least 500 mL) prior to hospital arrival. Secondary outcomes included in-hospital mortality, disposition, and length of stay. Multivariable logistic regression was used to compare outcomes between 6-month pre- and post-implementation periods (July-December 2021 and February-July 2022, respectively), adjusting for patient demographics, abnormal prehospital vital signs, and EMS transport interval. RESULTS: Of 1,180 eligible patients (552 in the pre-implementation period; 628 in the post-implementation period), the mean age was 72 years old, 45% were female, and 25% were minority race-ethnicity. Median (interquartile range) fluid volume (in mL) increased between the pre- and post-implementation periods (600 [400,1,000] and 850 [500-1,000], respectively). Goal fluid volume was achieved in 70% of pre-implementation patients and 82% of post-implementation patients. In adjusted analysis, post-implementation patients were significantly more likely to receive goal fluid volume than pre-implementation patients (adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.51-2.66). Pre-post in-hospital mortality was not significantly different (aOR 0.91, 95% CI 0.59-1.39). CONCLUSION: In a single EMS system, sepsis education and introduction of a rapid infusion device was associated with achieving goal fluid volume for suspected sepsis. Further research is needed to assess the clinical effectiveness of infusion device implementation to improve sepsis patient outcomes.

A tailored approach to horizon scanning for cancer medicines.

BACKGROUND: Horizon scanning (HS) is the systematic identification of emerging therapies to inform policy and decision-makers. We developed an agile and tailored HS methodology that combined multi-criteria decision analysis weighting and Delphi rounds. As secondary objectives, we aimed to identify new medicines in melanoma, non-small cell lung cancer and colorectal cancer most likely to impact the Australian government's pharmaceutical budget by 2025 and to compare clinician and consumer priorities in cancer medicine reimbursement. METHOD: Three cancer-specific clinician panels (total n = 27) and a consumer panel (n = 7) were formed. Six prioritisation criteria were developed with consumer input. Criteria weightings were elicited using the Analytic Hierarchy Process (AHP). Candidate medicines were identified and filtered from a primary database and validated against secondary and tertiary sources. Clinician panels participated in a three-round Delphi survey to identify and score the top five medicines in each cancer type. RESULTS: The AHP and Delphi process was completed in eight weeks. Prioritisation criteria focused on toxicity, quality of life (QoL), cost savings, strength of evidence, survival, and unmet need. In both curative and non-curative settings, consumers prioritised toxicity and QoL over survival gains, whereas clinicians prioritised survival. HS results project the ongoing prevalence of high-cost medicines. Since completion in October 2021, the HS has identified 70 % of relevant medicines submitted for Pharmaceutical Benefit Advisory Committee assessment and 60% of the medicines that received a positive recommendation. CONCLUSION: Tested in the Australian context, our method appears to be an efficient and flexible approach to HS that can be tailored to address specific disease types by using elicited weights to prioritise according to incremental value from both a consumer and clinical perspective. POLICY SUMMARY: Since HS is of global interest, our example provides a reproducible blueprint for adaptation to other healthcare settings that integrates consumer input and priorities.