Standardization of a silver stain to reveal mesoscale myelin in histological preparations of the mammalian brain.

BACKGROUND: The brain is built of neurons supported by myelin, a fatty substance that improves cellular communication. Noninvasive magnetic resonance imaging (MRI) is now able to measure brain structure like myelin and requires histological validation. NEW METHOD: Here we present work in small and large biomedical model mammals to standardize a silver impregnation method as a high-throughput histological myelin visualization procedure. Specifically, we built a new staining well plate to increase batch size, and then systematically varied the staining and clearing cycles to describe the staining response curve across taxa and conditions. We compared tissues fixed by immersion or perfusion, mounted versus free-floating, and cut as thicker or thinner slices, with two-weeks of post-fixation. RESULTS: The staining response curves show optimal staining with a single exposure across taxa when incubation and clearing epochs are held to within 3-9 min. We show that clearing was slower in mounted vs free-floating tissue, and that staining was faster and caused fracturing earlier in thinner sliced and smaller volumes of tissue. COMPARISON WITH EXISTING METHODS: We developed a batch processing approach to increase throughput while ensuring reproducibility and demonstrate the optimal conditions for fine myelinated fiber morphology visualization with short cycles (<9 minutes). CONCLUSIONS: We present our optimized protocol to reveal mesoscale neuroanatomical myelin content in histology across mammals. This standard staining procedure will facilitate multiscale analyses of myelin content across development as well as in the presence of injury or disease.

Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

Development of reference intervals for serum biochemistry and haematology of juvenile green sea turtles (Chelonia mydas) in a Thai rehabilitation centre.

No reference intervals for serum biochemistry and haematology of sea turtles in Thailand exists to assist veterinarians who are responsible for sea turtle health management and treatment. This study determined serum biochemistry and basic haematology of healthy juvenile green sea turtles (n = 92) in captivity in Thailand following the American Society for Veterinary Clinical Pathology (ASVCP), Quality Assurance and Laboratory Standards Committee (QALS) guidelines for the determination of reference intervals in veterinary species. Biochemistry tests, including blood urea nitrogen, creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were analysed using an IDEXX VetTest Chemistry Analyzer. Haematology parameters were measured manually using a microhaematocrit for packed cell volume (PCV), Neubauer counting chamber for red blood cell count and cyanmethemoglobin method for haemoglobin concentration. mean corpuscular volume and mean corpuscular haemoglobin concentration were calculated using the PCV, red blood cell count and haemoglobin. Turtles in this study were found to have higher mean values for PCV (28.70%), haemoglobin (92.13 g/L), mean corpuscular haemoglobin concentration (327.03 g/L), uric acid (247.15 µmol/L), alanine aminotransferase (16.53 IU/L), aspartate aminotransferase (209.44 IU/L), and alkaline phosphatase (245.08 IU/L) compared to sea turtles in Brazil. The reference intervals established using high numbers of healthy turtles in this study will assist veterinarians with diagnostic and treatment decisions when evaluating laboratory results for juvenile green sea turtles.

CTAD Task Force Paper: Neuropsychiatric Symptoms in AD: Clinical Trials Targeting Mild Behavioral Impairment: A Report from the International CTAD Task Force.

The International CTAD Task Force (TF) addressed challenges related to designing clinical trials for agitation in dementia, presenting accomplishments from the two previous TFs on neuropsychiatric symptoms (NPS). In addition, this TF proposed a paradigm shift in NPS assessment and management, presenting Mild Behavioral Impairment (MBI) as a clinical syndrome. MBI is marked by later-life emergent and persistent NPS in dementia-free older persons (ranging from cognitively unimpaired to subjective cognitive decline to mild cognitive impairment), which facilitates earlier detection and better prognostication of Alzheimer's disease (AD). The TF has made the following recommendations for incorporation of NPS into AD preventative trials: (1) clinical trials targeting improvement in MBI symptoms should be undertaken; (2) treatment trials for MBI should be disease specific and confirm the diagnosis of participants using biomarkers; trials should include measures sensitive to cognitive changes in preclinical AD, which can serve as outcome measures, in addition to changes in biomarker levels; (3) as a first step, pharmacotherapeutic trials should address the full MBI complex as well as the specific symptoms/domains that constitute MBI; (4) clinical trials using problem-adaptation psychotherapy to target affective MBI should be considered; and (5) MBI should be considered in AD trials of disease modifying therapies. The well-validated and widely-used MBI Checklist (MBI-C) is an appropriate symptom rating scale for these studies, as it was developed specifically to identify and measure MBI in dementia-free persons. Other scales such as the Neuropsychiatric Inventory (NPI) may be used, although administration at two timepoints may be necessary to operationalize the MBI criterion of symptom persistence.

Risk of Herpes Zoster Ophthalmicus After COVID-19 Vaccination in a Large US Health Care Claims Database.

PURPOSE: Herpes zoster ophthalmicus (HZO) after COVID-19 vaccination has been reported in numerous case studies. However, no large-scale epidemiologic studies have been conducted to date. The purpose of this study was to determine whether COVID-19 vaccination is associated with an increased risk of HZO. DESIGN: Retrospective before-and-after risk interval analysis. METHODS: RESULTS: In total, 1,959,157 patients received a dose of a COVID-19 vaccine during the study period and met eligibility criteria. A total of 80 individuals without a prior history of HZO were included in the analysis because they developed HZO in the risk or control period. Patients had a mean age of 54.0 years (SD = 12.3 years). There were 45 cases of HZO in the risk interval after COVID-19 vaccination. There was not an increased risk of HZO after vaccination with BNT162b2 (IRR = 0.90, 95% CI: 0.49-1.69, P = .74), mRNA-1273 (IRR = 0.74, 95% CI: 0.36-1.54, P = .42), or Ad26.COV2.S (IRR = 0.50, 95% CI: 0.07-2.56, P = .42). CONCLUSIONS: This study found no evidence of increased risk of HZO after COVID-19 vaccination, providing reassurance for patients and providers who may be concerned about the safety profile of the COVID-19 vaccines.

Risk of Noninfectious Uveitis after Coronavirus Disease 2019 Vaccination in a United States Claims Database.

PURPOSE: To assess noninfectious uveitis (NIU) risk after coronavirus disease 2019 (COVID-19) vaccination in patients without a history of uveitis. DESIGN: A retrospective matched cohort study and self-controlled case series (SCCS) analysis using a longitudinal data asset with claims data from the OptumLabs Data Warehouse from December 11, 2020, through November 30, 2021. PARTICIPANTS: The matched cohort analysis included patients continuously enrolled for 730 days before December 11, 2020, who received a COVID-19 vaccination during the study period. This COVID-19-vaccinated group was matched to a COVID-19-unvaccinated historical cohort enrolled in 2018 and 2019. The SCCS design included individuals from the vaccinated cohort who experienced an NIU event during the study period. Enrollees with a history of uveitis were excluded. METHODS: Hazard ratios (HRs) were calculated using Cox proportional hazards models in the matched cohort design. Incidence rate ratios (IRRs) comparing NIU incidence in exposed risk periods after vaccination and unexposed control periods within individuals were calculated using conditional Poisson regression models in the SCCS design. Models were adjusted for age, recent receipt of non-COVID-19 vaccinations, corticosteroid or immunosuppressive use, and smoking history. Subgroup analyses were conducted by vaccination type and age group. MAIN OUTCOME MEASURES: Rates of NIU identified with International Classification of Diseases, Tenth Revision, codes. RESULTS: The matched cohort analysis included 4 611 378 patients, with 2 305 689 per cohort. The adjusted HR comparing NIU incidence in the COVID-19-vaccinated and unvaccinated cohort was 0.91 (95% confidence interval [CI], 0.75-1.10; P = 0.33). The SCCS analysis included 686 patients. The IRR comparing NIU risk after vaccination with risk during control intervals was 1.05 (95% CI, 0.89-1.23; P = 0.57). An increased risk was found in the subgroup aged 5 to 44 years (IRR, 1.40; 95% CI, 1.04-1.87; P = 0.024). CONCLUSIONS: The matched cohort and SCCS analyses did not detect increased NIU risk after COVID-19 vaccination overall in individuals without history of uveitis, providing reassurance about the vaccine's safety. The finding of increased risk in the youngest subgroup suggests heightened immune responses in younger individuals, warranting further investigation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.

BACKGROUND: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. MAIN BODY: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. CONCLUSION: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

Gravity complexes as a focus of seafloor fluid seepage: the Rio Grande Cone, SE Brazil.

Seafloor methane emissions can affect Earth's climate and ocean chemistry. Vast quantities of methane formed by microbial decomposition of organic matter are locked within gas hydrate and free gas on continental slopes, particularly in large areas with high sediment accumulations such as deep-sea fans. The release of methane in slope environments has frequently been associated with dissociation of gas hydrates near the edge of the gas hydrate stability zone on the upper slope, with discharges in greater water depths less understood. Here we show, using data from the Rio Grande Cone (western South Atlantic), that the intrinsic, gravity-induced downslope collapse of thick slope sediment accumulations creates structures that serve as pathways for gas migration, unlocking methane and causing seafloor emissions via giant gas flares in the water column. The observed emissions in the study region (up to 310 Mg year-1) are three times greater than estimates for the entire US North Atlantic margin and reveal the importance of collapsing sediment accumulations for ocean carbon cycling. Similar outgassing systems on the Amazon and Niger fans suggest that gravity tectonics on passive margins is a common yet overlooked mechanism driving massive seafloor methane emissions in sediment-laden continental slopes.

Cerambycid Pheromones Attract Predators Temnoscheila virescens (Coleoptera: Trogossitidae), Chariessa pilosa (Coleoptera: Cleridae), and Apiomerus crassipes (Hemiptera: Reduviidae).

In 2011-2013, we determined the interactive effects of the cerambycid pheromones racemic syn-2,3-hexanediol, racemic 3-hydroxyhexan-2-one, and racemic 3-hydroxyoctan-2-one on trap catches of predators associated with bark and woodboring beetles in north Georgia and South Carolina. Temnoscheila virescens (F.) (Coleoptera: Trogossitidae) was attracted to traps baited with 3-hydroxyhexan-2-one; ethanol enhanced attraction. Traps baited with syn-2,3-hexanediol attracted Chariessa pilosa (Forster) (Coleoptera: Cleridae); attraction was interrupted by 3-hydroxyhexan-2-one. An assassin bug Apiomerus crassipes (F.) (Hemiptera: Reduviidae) was attracted to traps baited with 3-hydroxyhexan-2-one and/or 3-hydroxyoctan-2-one. Ethanol had no effect on trap catches of C. pilosa and A. crassipes. We compared response profiles of these predators to those of longhorn beetles captured in these same studies to provide insights on possible ecological interactions between these species.

Implementing post-normal science with or for EU policy actors: using quantitative story-telling.

There is increasing recognition of the wicked nature of the intertwined climate, biodiversity and economic crises, and the need for adaptive, multi-scale approaches to understanding the complexity of both the problems and potential responses. Most science underpinning policy responses to sustainability issues, however, remains overtly apolitical and focussed on technical innovation; at odds with a critical body of literatures insisting on the recognition of systemic problem framing when supporting policy processes. This paper documents the experience of implementing a mixed method approach called quantitative story-telling (QST) to policy analysis that explicitly recognises this normative dimension, as the methodology is part of a post-normal science (PNS) toolkit. The authors reflect on what was learnt when considering how QST fared as a tool for science-policy interaction, working with European Union (EU) level policy actors interested in sustainable agriculture and sustainable development goal 2. These goals-also known as UN Agenda 2030-are the latest institutionalisation of the pursuit of sustainable development and the EU has positioned itself as taking a lead in its implementation. Thus, the paper illustrates our experience of using PNS as an approach to science policy interfaces in a strategic policy context; and illustrates how the challenges identified in the science-policy literature are amplified when working across multiple policy domains and taking a complex systems approach. Our discussion on lessons learnt may be of interest to researchers seeking to work with policy-makers on complex sustainability issues.

Midterm outcomes of aortic root surgery in patients with Marfan syndrome: A prospective, multicenter, comparative study.

OBJECTIVE: The objective of this study was to compare midterm outcomes of aortic valve-replacing root replacement (AVR) and aortic valve-sparing root replacement (AVS) operations in patients with Marfan syndrome. METHODS: Patients who met strict Ghent diagnostic criteria for Marfan syndrome and who underwent either AVR or AVS between March 1, 2005 and December 31, 2010 were enrolled in a 3-year follow-up prospective, multicenter, international registry study; the study was subsequently amended to include 20-year follow-up. Enrollees were followed clinically and echocardiographically. RESULTS: Of the 316 patients enrolled, 77 underwent AVR and 239 underwent AVS; 214 gave reconsent for 20-year follow-up. The median clinical follow-up time for surviving patients was 64 months (interquartile range, 42-66 months). Survival rates for the AVR and AVS groups were similar at 88.2% ± 4.4% and 95.0% ± 1.5%, respectively (P = .1). Propensity score-adjusted competing risk modeling showed associations between AVS and higher cumulative incidences of major adverse valve-related events, valve-related morbidity, combined structural valve deterioration and nonstructural valve dysfunction, and aortic regurgitation ≥2+ (all P < .01). No differences were found for reintervention (P = .7), bleeding (P = .2), embolism (P = .3), or valve-related mortality (P = .8). CONCLUSIONS: Five years postoperatively, major adverse valve-related events and valve-related morbidity were more frequent after AVS than after AVR procedures, primarily because of more frequent aortic valve dysfunction. No between-group differences were found in rates of survival, valve-related mortality, reintervention on the aortic valve, or bleeding. We plan to follow this homogenous cohort for 20 years after aortic root replacement.

Inter-observer variability of expert-derived morphologic risk predictors in aortic dissection.

OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning. METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a composite of three expert-observers (observers 2-4) using a standardized workflow. A second inter-observer variability assessment on 30 out of the 47 CTA scans compared observers 3 and 4 with a constrained, standardized workflow. A third inter-observer variability assessment was done after specialized training and tested between observers 3 and 4 in an external population of 25 CTA scans. Inter-observer agreement was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: Pre-training ICCs of the four morphologic features ranged from 0.04 (-0.05 to 0.13) to 0.68 (0.49-0.81) between observer 1 and observers 2-4 and from 0.50 (0.32-0.69) to 0.89 (0.78-0.95) between observers 3 and 4. ICCs improved after training ranging from 0.69 (0.52-0.87) to 0.97 (0.94-0.99), and Bland-Altman analysis showed decreased bias and limits of agreement. CONCLUSIONS: Manual morphologic feature measurements on CTA images can be optimized resulting in improved inter-observer reliability. This is essential for robust ground-truth determination for machine learning models. KEY POINTS: • Clinical fashion manual measurements of aortic CTA imaging features showed poor inter-observer reproducibility. • A standardized workflow with standardized training resulted in substantial improvements with excellent inter-observer reproducibility. • Robust ground truth labels obtained manually with excellent inter-observer reproducibility are key to develop reliable machine learning models.

Assessment of Herpes Zoster Risk Among Recipients of COVID-19 Vaccine.

Importance: Herpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk. Objective: To assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection. Design, Setting, and Participants: This cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the early pandemic period (March 1, 2020, to November 30, 2020). Data were obtained from Optum Labs Data Warehouse, a US national deidentified claims-based database. A total of 2 039 854 individuals who received any dose of a COVID-19 vaccine with emergency use authorization (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], or Ad26.COV2.S [Johnson & Johnson]) from December 11, 2020, through June 30, 2021, were eligible for inclusion. Individuals included in the SCRI analysis were a subset of the COVID-19-vaccinated cohort who had herpes zoster during either a risk or control interval. Exposures: Any dose of a COVID-19 vaccine. Main Outcomes and Measures: Incident herpes zoster, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and a prescription of a new antiviral medication or a dose increase in antiviral medication within 5 days of diagnosis. Results: Among 2 039 854 individuals who received any dose of a COVID-19 vaccine during the study period, the mean (SD) age was 43.2 (16.3) years; 1 031 149 individuals (50.6%) were female, and 1 344 318 (65.9%) were White. Of those, 1451 patients (mean [SD] age, 51.6 [12.6] years; 845 [58.2%] female) with a herpes zoster diagnosis were included in the primary SCRI analysis. In the SCRI analysis, COVID-19 vaccination was not associated with an increased risk of herpes zoster after adjustment (incidence rate ratio, 0.91; 95% CI, 0.82-1.01; P = .08). In the supplementary cohort analysis, COVID-19 vaccination was not associated with a higher risk of herpes zoster compared with influenza vaccination in the prepandemic period (first dose of COVID-19 vaccine: hazard ratio [HR], 0.78 [95% CI, 0.70-0.86; P < .001]; second dose of COVID-19 vaccine: HR, 0.79 [95% CI, 0.71-0.88; P < .001]) or the early pandemic period (first dose of COVID-19 vaccine: HR, 0.89 [95% CI, 0.80-1.00; P = .05]; second dose: HR, 0.91 [95% CI, 0.81-1.02; P = .09]). Conclusions and Relevance: In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.

Association of Thoracic Aortic Aneurysm Size With Long-term Patient Outcomes: The KP-TAA Study.

Importance: The risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making. Objective: To evaluate the association of TAA size with outcomes in nonsyndromic patients in a large non-referral-based health care delivery system. Design, Setting, and Participants: The Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was a retrospective cohort study at Kaiser Permanente Northern California, a fully integrated health care delivery system insuring and providing care for more than 4.5 million persons. Nonsyndromic patients from a regional TAA safety net tracking system were included. Imaging data including maximum TAA size were merged with electronic health record (EHR) and comprehensive death data to obtain demographic characteristics, comorbidities, medications, laboratory values, vital signs, and subsequent outcomes. Unadjusted rates were calculated and the association of TAA size with outcomes was evaluated in multivariable competing risk models that categorized TAA size as a baseline and time-updated variable and accounted for potential confounders. Data were analyzed from January 2018 to August 2021. Exposures: TAA size. Main Outcomes and Measures: Aortic dissection (AD), all-cause death, and elective aortic surgery. Results: Of 6372 patients with TAA identified between 2000 and 2016 (mean [SD] age, 68.6 [13.0] years; 2050 female individuals [32.2%] and 4322 male individuals [67.8%]), mean (SD) initial TAA size was 4.4 (0.5) cm (828 individuals [13.0% of cohort] had initial TAA size 5.0 cm or larger and 280 [4.4%] 5.5 cm or larger). Rates of AD were low across a mean (SD) 3.7 (2.5) years of follow-up (44 individuals [0.7% of cohort]; incidence 0.22 events per 100 person-years). Larger initial aortic size was associated with higher risk of AD and all-cause death in multivariable models, with an inflection point in risk at 6.0 cm. Estimated adjusted risks of AD within 5 years were 0.3% (95% CI, 0.3-0.7), 0.6% (95% CI, 0.4-1.3), 1.5% (95% CI, 1.2-3.9), 3.6% (95% CI, 1.8-12.8), and 10.5% (95% CI, 2.7-44.3) in patients with TAA size of 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm, and 6.0 cm or larger, respectively, in time-updated models. Rates of the composite outcome of AD and all-cause death were higher than for AD alone, but a similar inflection point for increased risk was observed at 6.0 cm. Conclusions and Relevance: In a large sociodemographically diverse cohort of patients with TAA, absolute risk of aortic dissection was low but increased with larger aortic sizes after adjustment for potential confounders and competing risks. Our data support current consensus guidelines recommending prophylactic surgery in nonsyndromic individuals with TAA at a 5.5-cm threshold.

Discharge Opioids are Unnecessary Following Radical Cystectomy.

OBJECTIVE: To show that zero-opioid discharges after both open and robotic cystectomy are feasible and to examine the impact of zero-opioid discharges on patient interaction with the physician's office. MATERIALS AND METHODS: One hundred seven patients who underwent either open or robotic radical cystectomy from March 1, 2020 to December 30, 2020 were identified. Patient demographics, perioperative data, and 30 day pain related outcomes including phone calls, office visits, requests for pain medication, emergency department visits, and readmissions were abstracted from the chart. We then examined variables associated with a zero-opioid discharge. RESULTS: Thirty-two patients were discharged with an opioid prescription (Median Oral Morphine Equivalents Prescribed = 90) and 75 were discharged without an opioid prescription. On regression analysis, age (OR 1.07, 95% CI [1.02-1.12]) and pathology (OR 0.36, 95% CI[0.14-0.9]) remained significantly associated with post-operative opioid prescriptions. There were no differences in the percent of patients presenting to the emergency department, being readmitted, calling the office, calling the office regarding pain, or requesting opioid prescriptions within 30 days of discharge, or the number of post-operative office visits (P >.05 for all). CONCLUSION: Patients can safely be discharged home without opioids following cystectomy, regardless of robotic or open approach. Age and pathology are predictors of the need for an opioid prescription on discharge. These patients did not have increased follow-up visits, phone calls, or requests for pain medication.

TROG 14.04: Multicentre Study of Feasibility and Impact on Anxiety of DIBH in Breast Cancer Patients.

AIMS: The aim of TROG 14.04 was to assess the feasibility of deep inspiration breath hold (DIBH) and its impact on radiation dose to the heart in patients with left-sided breast cancer undergoing radiotherapy. Secondary end points pertained to patient anxiety and cost of delivering a DIBH programme. MATERIALS AND METHODS: The study comprised two groups - left-sided breast cancer patients engaging DIBH and right-sided breast cancer patients using free breathing through radiotherapy. The primary end point was the feasibility of DIBH, defined as left-sided breast cancer patients' ability to breath hold for 15 s, decrease in heart dose in DIBH compared with the free breathing treatment plan and reproducibility of radiotherapy delivery using mid-lung distance (MLD) assessed on electronic portal imaging as the surrogate. The time required for treatment delivery, patient-reported outcomes and resource requirement were compared between the groups. RESULTS: Between February and November 2018, 32 left-sided and 30 right-sided breast cancer patients from six radiotherapy centres were enrolled. Two left-sided breast cancer patients did not undergo DIBH (one treated in free breathing as per investigator choice, one withdrawn). The mean heart dose was reduced from 2.8 Gy (free breathing) to 1.5 Gy (DIBH). Set-up reproducibility in the first week of treatment assessed by MLD was 1.88 ± 1.04 mm (average ± 1 standard deviation) for DIBH and 1.59 ± 0.93 mm for free breathing patients. Using a reproducibility cut-off for MLD of 2 mm (1 standard deviation) as per study protocol, DIBH was feasible for 67% of DIBH patients. Radiotherapy delivery using DIBH took about 2 min longer than for free breathing. Anxiety was not significantly different in DIBH patients and decreased over the course of treatment in both groups. CONCLUSION: Although DIBH was shown to require about 2 min longer per treatment slot, it has the potential to reduce heart dose in left-sided breast cancer patients by nearly a half, provided careful assessment of breath hold reproducibility is carried out.

Association between Immunosuppressive Drugs and Coronavirus Disease 2019 Outcomes in Patients with Noninfectious Uveitis in a Large US Claims Database.

PURPOSE: To determine the dose-dependent risk of systemic corticosteroids (SCs) and the risk of other immunosuppressive therapies on coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in patients with noninfectious uveitis (NIU). DESIGN: A retrospective cohort study from January 20, 2020, to December 31, 2020 (an era before widespread COVID-19 vaccination), using the Optum Labs Data Warehouse, a US national de-identified claims database. PARTICIPANTS: Patients who had at least 1 NIU diagnosis from January 1, 2017. METHODS: Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models, with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of SC exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models as a continuous variable, in addition to the dichotomous variable. MAIN OUTCOME MEASURES: Incidence rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death. RESULTS: This study included 52 286 NIU patients of whom 12 000 (23.0%) were exposed to immunosuppressive medications during the risk period. In adjusted models, exposure to SCs was associated with increased risk of COVID-19 infection (HR, 2.66; 95% confidence interval [CI], 2.19-3.24; P < 0.001), hospitalization (HR, 3.26; 95% CI, 2.46-4.33; P < 0.001), and in-hospital death (HR, 1.99; 95% CI, 0.93-4.27; P = 0.08). Furthermore, incremental increases in the dosage of SCs were associated with a greater risk for these outcomes. Although tumor necrosis factor-α (TNF-α) inhibitors were associated with an increased risk of infection (HR, 1.48; 95% CI, 1.08-2.04; P = 0.02), other immunosuppressive treatments did not increase the risk of COVID-19 infection, hospitalization, or death. CONCLUSIONS: This study from an era before widespread COVID-19 vaccination demonstrates that outpatient SC exposure is associated with greater risk of COVID-19 infection and severe outcomes in patients with NIU. Future studies should evaluate the impact of immunosuppression in vaccinated NIU patients. Limiting exposure to SCs and use of alternative therapies may be warranted.

Cerambycid Pheromones 3,2-Hydroxyketones Affect Catches of Some Bark and Ambrosia Beetles (Coleoptera: Curculionidae) in Ethanol-Baited Multiple-Funnel Traps in Southeastern United States.

In 2012-2013, we assessed the interactive effects of the cerambycid pheromones syn-2,3-hexanediol, 3-hydroxyhexan-2-one, and 3-hydroxyoctan-2-one on catches of bark and ambrosia beetles (Coleoptera: Curculionidae) in ethanol-baited multiple-funnel traps in north Georgia and South Carolina. We found that catches for nine of eleven species of ambrosia beetles in ethanol-baited traps were either unaffected or enhanced by the addition of 3,2-hydroxyketones. Similarly catches of five species of bark beetles were either unaffected or enhanced by the addition of 3,2-hydroxyketones. In particular, catches of Xylosandrus crassiusculus (Motschulsky), Cnestus mutilatus (Blandford), and Monarthrum fasciatum (Say) in ethanol-baited traps increased with the addition of 3-hydroxyhexan-2-one and/or 3-hydroxyoctan-2-one. Catches of the bark beetles Hylocurus rudis (LeConte) and Hypothenemus rotundicollis (Eichhoff) were enhanced by the addition of 3-hydroxyhexan-2-one and 3-hydroxyoctan-2-one, respectively. syn-2,3-Hexanediol had no effect on catches of bark and ambrosia beetles in ethanol-baited traps. Our data provide support for the use of ethanol + cerambycid pheromones for targeting non-native species of bark and ambrosia beetles as well as cerambycids in detection programs.