The reliability of the College of Intensive Care Medicine of Australia and New Zealand "Hot Case" examination.

BACKGROUND: High stakes examinations used to credential trainees for independent specialist practice should be evaluated periodically to ensure defensible decisions are made. This study aims to quantify the College of Intensive Care Medicine of Australia and New Zealand (CICM) Hot Case reliability coefficient and evaluate contributions to variance from candidates, cases and examiners. METHODS: This retrospective, de-identified analysis of CICM examination data used descriptive statistics and generalisability theory to evaluate the reliability of the Hot Case examination component. Decision studies were used to project generalisability coefficients for alternate examination designs. RESULTS: Examination results from 2019 to 2022 included 592 Hot Cases, totalling 1184 individual examiner scores. The mean examiner Hot Case score was 5.17 (standard deviation 1.65). The correlation between candidates' two Hot Case scores was low (0.30). The overall reliability coefficient for the Hot Case component consisting of two cases observed by two separate pairs of examiners was 0.42. Sources of variance included candidate proficiency (25%), case difficulty and case specificity (63.4%), examiner stringency (3.5%) and other error (8.2%). To achieve a reliability coefficient of > 0.8 a candidate would need to perform 11 Hot Cases observed by two examiners. CONCLUSION: The reliability coefficient for the Hot Case component of the CICM second part examination is below the generally accepted value for a high stakes examination. Modifications to case selection and introduction of a clear scoring rubric to mitigate the effects of variation in case difficulty may be helpful. Increasing the number of cases and overall assessment time appears to be the best way to increase the overall reliability. Further research is required to assess the combined reliability of the Hot Case and viva components.

How Reliable are Single-Question Workplace-Based Assessments in Surgery?

OBJECTIVE: Workplace-based assessments (WBAs) play an important role in the assessment of surgical trainees. Because these assessment tools are utilized by a multitude of faculty, inter-rater reliability is important to consider when interpreting WBA data. Although there is evidence supporting the validity of many of these tools, inter-reliability evidence is lacking. This study aimed to evaluate the inter-rater reliability of multiple operative WBA tools utilized in general surgery residency. DESIGN: General surgery residents and teaching faculty were recorded during 6 general surgery operations. Nine faculty raters each reviewed 6 videos and rated each resident on performance (using the Society for Improving Medical Professional Learning, or SIMPL, Performance Scale as well as the operative performance rating system (OPRS) Scale), entrustment (using the ten Cate Entrustment-Supervision Scale), and autonomy (using the Zwisch Scale). The ratings were reviewed for inter-rater reliability using percent agreement and intraclass correlations. PARTICIPANTS: Nine faculty members viewed the videos and assigned ratings for multiple WBAs. RESULTS: Absolute intraclass correlation coefficients for each scale ranged from 0.33 to 0.47. CONCLUSIONS: All single-item WBA scales had low to moderate inter-rater reliability. While rater training may improve inter-rater reliability for single observations, many observations by many raters are needed to reliably assess trainee performance in the workplace.

Redefining FLASH RT: the impact of mean dose rate and dose per pulse in the gastrointestinal tract.

Background: The understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited. Purpose: We sought to evaluate how the magnitude of radiation-induced gastrointestinal (GI) toxicity (RIGIT) depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP). Methods: C57BL/6J mice were subjected to total abdominal irradiation (11-14 Gy single fraction) under conventional irradiation (low DPP and low MDR, CONV) and various combinations of DPP and MDR up to ultra-high-dose-rate (UHDR) beam conditions. The effects of DPP were evaluated for DPPs of 1-6 Gy while the total dose and MDR were kept constant; the effects of MDR were evaluated for the range 0.3- 1440 Gy/s while the total dose and DPP were kept constant. RIGIT was quantified in non-tumor-bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay. Results: Within each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to better sparing of regenerating crypts, with a more prominent effect seen at 12 and 14 Gy TAI. However, at fixed DPPs >4 Gy, similar sparing of crypts was demonstrated irrespective of MDR (from 0.3 to 1440 Gy/s). At a fixed high DPP of 4.7 Gy, survival was equivalently improved relative to CONV for all MDRs from 0.3 Gy/s to 104 Gy/s, but at a lower DPP of 0.93 Gy, increasing MDR produced a greater survival effect. We also confirmed that high DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model. Conclusions: This study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high DPP and UHDR appeared independently sufficient to produce FLASH sparing of GI toxicity, while isoeffective tumor response was maintained across all conditions.

A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker with Positive Signal Contrast for Image-Guided Radiation Therapy.

BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA. METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 film, with FMs oriented either perpendicular to or parallel with the beam axis. We also tested the performance of NOVA-FMs in a patient. RESULTS: NOVA-FMs were positively visualized on all 4 imaging modalities tested. The rSAL on CT was 0.750 ± 0.335 for 2-mm reconstructed slices. In F-tests, PDP was associated with marker type and depth of measurement (p < 10-6); at 5-mm depth, PDP was significantly greater for the G-FM (12.9%, p = 10-6) and C-FM (6.0%, p = 0.011) than NOVA (4.5%). EBRT planning with MRI/CT image co-registration and daily alignments using NOVA-FMs in a patient was feasible and reproducible. CONCLUSIONS: NOVA-FMs were positively visible and produced less PDP than G-FMs or C-FMs. NOVA-FMs facilitated MRI/CT fusion and identification of regions of interest.

Factors influencing receipt and time to treatment of immunotherapy relative to chemotherapy in stage III and stage IV melanoma.

BACKGROUND: Immunotherapies have changed the landscape of late-stage melanoma; however, data evaluating timely access to immunotherapy are lacking. METHODS: A retrospective cohort study utilizing the National Cancer Database was conducted. Stage III and IV melanoma cases diagnosed between 2011 and 2018 that received systemic treatment with either immunotherapy or chemotherapy were included. Chemotherapy included BRAF/MEK inhibitors. Multivariable logistic regression models were utilized to evaluate factors associated with the likelihood of receiving immunotherapy as primary systemic treatment relative to chemotherapy; additionally, Cox proportional hazards models were utilized to incorporate time from diagnosis to primary systemic therapy into the analysis. RESULTS: The study population was comprised of 14,446 cases. The cohort included 12,053 (83.4%) immunotherapy and 2393 (16.6%) chemotherapy cases. In multivariable logistic regression analysis, factors significantly associated with immunotherapy receipt included population density, circle distance, year of diagnosis, Breslow thickness, and cancer stage. Immunotherapy timing was evaluated using multivariable Cox regression analysis. Minorities were less likely to receive timely immunotherapy than non-Hispanic Whites (HR 0.83, CI 0.74-0.93, p = 0.001). Patients at circle distances of 10-49 miles (HR 0.94, CI 0.89-0.99, p = 0.02) and ≥50 miles (HR 0.83, CI 0.77-0.90, p < 0.001) were less likely to receive timely immunotherapy. CONCLUSION: Patients traveling ≥10 miles and minorities have a decreased likelihood of receiving timely immunotherapy administration for primary systemic treatment. Future research is needed to identify what barriers and approaches can be leveraged to address these inequities.

Modeling geographic vaccination strategies for COVID-19 in Norway.

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.

Utility of Dermoscopy Training in Improving Diagnostic Accuracy of Skin Lesions Among Physician Assistant Students.

INTRODUCTION: Patients often first present to their primary care provider for skin lesion concerns, and dermoscopy is a tool that enhances diagnostic acumen of both malignant and benign skin lesions. Physician assistants (PAs) frequently serve as primary care and dermatology providers, but to our knowledge, no current research on dermoscopy expertise with PAs exists. We hypothesize that PA students could be taught dermoscopy based on the triage amalgamated dermoscopic algorithm (TADA) to increase their diagnostic skill, as previously shown with medical students. METHODS: Dermoscopy was taught to first-year PA students at all 5 PA programs in the state of Minnesota. The training was 50 minutes in length and focused on the fundamentals of the TADA method. Physician assistant students participated in a pretraining and post-training test, consisting of 30 dermoscopic images. RESULTS: A total of 139/151 (92%) PA students completed both the pretraining and post-training tests. Overall, mean scores for all students increased significantly ( P < .0001) after dermoscopy training was given (18.5 ± 7.1 vs. 23.8 ± 6.7). CONCLUSION: Our study demonstrates that after TADA training, PA students improved their ability to assess dermoscopy images of both skin cancer and benign lesions accurately, suggesting that PAs can be trained as novice dermoscopists and provide better dermatologic care to patients. We strongly encourage integration of dermoscopy into didactic education across PA programs. Implementing a dermoscopy curriculum in established PA programs will enable future PAs to provide better clinical care when evaluating skin lesions.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Targeted RNA Sequencing Highlights a Diverse Genomic and Morphologic Landscape in Low-grade Endometrial Stromal Sarcoma, Including Novel Fusion Genes.

Low-grade endometrial stromal sarcoma (LGESS) represents a morphologically and genetically heterogenous mesenchymal neoplasm. Previous work has shown that approximately half of LGESS are characterized by JAZF1::SUZ12 gene fusions, while a smaller proportion involves rearrangement of other genes. However, a subset of cases has no known genetic abnormalities. To better characterize the genomic landscape of LGESS, we interrogated a cohort with targeted RNA sequencing (RNA-Seq). Cases previously diagnosed as low-grade endometrial stromal neoplasia (n=51) were identified and re-reviewed for morphology and subjected to RNA-Seq, of which 47 were successfully sequenced. The median patient age was 49 years (range: 19 to 85). The most commonly detected fusions were JAZF1::SUZ12 (n=26, 55%) and BRD8::PHF1 (n=3, 6%). In addition to the usual/typical LGESS morphology, some JAZF1::SUZ12 fusion tumors showed other morphologies, including fibrous, smooth muscle, sex-cord differentiation, and myxoid change. Novel translocations were identified in 2 cases: MEAF6::PTGR2 and HCFC1::PHF1 . Ten tumors (21%) had no identifiable fusion, despite a similar morphology and immunophenotype to fusion-positive cases. This suggests that a subset of cases may be attributable to fusion products among genes that are not covered by the assay, or perhaps altogether different molecular mechanisms. In all, these findings confirm that RNA-Seq is a potentially useful ancillary test in the diagnosis of endometrial stromal neoplasms and highlight their diverse morphology.

Timing's not everything: Immediate and delayed feedback are equally beneficial for performance in formative multiple-choice testing.

INTRODUCTION: Test-enhanced learning (TEL) is an impactful teaching and learning strategy that prioritises active learner engagement through the process of regular testing and reviewing. While it is clear that meaningful feedback optimises the effects of TEL, the ideal timing of this feedback (i.e. immediate or delayed) in a medical education setting is unclear. METHOD: Forty-one second-year medical students were recruited from the University of Melbourne. Participants were given a multiple-choice question test with a mix of immediate (i.e. post-item) and delayed (i.e. post-item-block) conceptual feedback. Students were then tested on near and far transfer items during an immediate post-test, and at a one-week follow-up. RESULTS: A logistic mixed effects model was used to predict the probability of successful near and far transfer. As expected, participants in our study tended to score lower on far transfer items than they did on near transfer items. In addition, correct initial response on a parent question predicted subsequent correct responding. Contrary to our hypotheses, the feedback timing effect was non-significant-there was no discernible difference between feedback delivered immediately versus delayed feedback. DISCUSSION: The findings of this study suggest that the timing of feedback delivery (post-item versus post-item-block) does not influence the efficacy of TEL in this medical education setting. We therefore suggest that educators may consider practical factors when determining appropriate TEL feedback timing in their setting.

Evidence for a maintenance cost for birds maintaining highly flexible basal, but not summit, metabolic rates.

Reversible phenotypic flexibility allows organisms to better match phenotypes to prevailing environmental conditions and may produce fitness benefits. Costs and constraints of phenotypic flexibility may limit the capacity for flexible responses but are not well understood nor documented. Costs could include expenses associated with maintaining the flexible system or with generating the flexible response. One potential cost of maintaining a flexible system is an energetic cost reflected in the basal metabolic rate (BMR), with elevated BMR in individuals with more flexible metabolic responses. We accessed data from thermal acclimation studies of birds where BMR and/or Msum (maximum cold-induced metabolic rate) were measured before and after acclimation, as a measure of metabolic flexibility, to test the hypothesis that flexibility in BMR (ΔBMR), Msum (ΔMsum), or metabolic scope (Msum - BMR; ΔScope) is positively correlated with BMR. When temperature treatments lasted at least three weeks, three of six species showed significant positive correlations between ΔBMR and BMR, one species showed a significant negative correlation, and two species showed no significant correlation. ΔMsum and BMR were not significantly correlated for any species and ΔScope and BMR were significantly positively correlated for only one species. These data suggest that support costs exist for maintaining high BMR flexibility for some bird species, but high flexibility in Msum or metabolic scope does not generally incur elevated maintenance costs.

Analgesic effect of oral paracetamol 1000 mg/ibuprofen 400 mg, paracetamol 1000 mg/codeine 60 mg, paracetamol 1000 mg/ibuprofen 400 mg/codeine 60 mg, or placebo on acute postoperative pain: a single-dose, randomized, and double-blind study.

PURPOSE: Combining analgesics with different mechanisms of action may increase the analgesic efficacy. The multidimensional pharmacodynamic profiles of ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 400 mg/paracetamol 1000 mg/codeine 60 mg, and paracetamol 1000 mg/codeine 60 mg and placebo were compared. METHODS: A randomized, double-blind, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 200 patients of both sexes and homogenous ethnicity after third molar surgery (mean age 24 years, range 19-30 years). Primary outcome was sum pain intensity over 6 h (SPI). Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference (SPID), maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat, prevent remedication and harm values, adverse effects, and patient-reported outcome measure (PROM). RESULTS: Analgesia following ibuprofen and paracetamol combination with or without codeine was comparable. Both were better than paracetamol combined with codeine. Secondary variables supported this finding. Post hoc analysis of SPI and SPID revealed a sex/drug interaction trend in the codeine-containing groups where females experienced less analgesia. PROM showed a significant sex/drug interaction in the paracetamol and codeine group, but not in the other codeine-containing group. Especially females reported known and mild side effects in the codeine-containing groups. CONCLUSION: Codeine added to ibuprofen/paracetamol does not seem to add analgesia in a sex-mixed study population. Sex may be a confounding factor when testing weak opioid analgesics such as codeine. PROM seems to be more sensitive than traditional outcome measures. TRIAL REGISTRATION: ClinicalTrials.gov June 2009 NCT00921700.

Episiotomy-assisted Incarcerated Femoral Nail Removal: Technical Note.

Introduction: Incarceration of intramedullary nails can pose a significant challenge. There are many reported techniques of nail removal, but when these fail, it can be difficult to determine how to proceed. Here, it is shown that a proximal femoral episiotomy can be used with great effect. Case Report: 64-year-old male developed hip arthritis. The patient had a solid antegrade femoral nail placed 22 years ago that required removal for a hip arthroplasty. A proximal femoral episiotomy-assisted approach was used with good results and patient outcome. Conclusion: There are several well described techniques to assist with incarcerated nail removal that all trauma surgeons should be familiar with. Proximal femoral episiotomy is a useful technique, every surgeon should have in their arsenal.

Improving RNA Fusion Call Confidence and Reliability in Molecular Diagnostic Testing.

Next-generation sequencing is a superior method for detecting known and novel RNA fusions in formalin-fixed, paraffin-embedded tissue over fluorescence in situ hybridization and RT-PCR. However, confidence in fusion calling and true negatives may be compromised by poor RNA quality. Using a commercial panel of 507 genes and the recommended 3-million read threshold to accept results, two cases yielded false negatives while exceeding this recommendation during clinical validation. To develop a reliable quality control metric that better reflects internal sample quality and improves call confidence, gene expression across 361 patient tumor samples was evaluated to derive a set of 15 genes to serve as a proxy quality control (pQC). These 15 genes were assessed for their normalized expression using the sequencing data from each case and selected for robustness. A threshold of 11 pQC genes produced a 4.71% fail rate, selected for stringency as an acceptable level of repeated testing in the clinical setting, minimizing false-negative calls. To increase the chance that low-quality samples pass pQC, a revision to the library preparation method was also tested, with 75% of previously failed samples passing pQC on resequencing by increasing cDNA input. Taken together, a next-generation sequencing analysis quality control tool is presented that serves as a surrogate for housekeeping genes and improves confidence in fusion calls.

Outcomes after PD-103 versus I-125 for low dose rate prostate brachytherapy monotherapy: An international, multi-institutional study.

BACKGROUND AND PURPOSE: Pd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression. RESULTS: Compared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971). CONCLUSIONS: Pd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125.