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Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Abstract Climate change threatens the resource adequacy of future power systems. Existing research and practice lack frameworks for identifying decarbonization pathways that are robust to climate‐related uncertainty. We create such an analytical framework, then use it to assess the robustness of alternative pathways to achieving 60% emissions reductions from 2022 levels by 2040 for the Western U.S. power system. Our framework integrates power system planning and resource adequacy models with 100 climate realizations from a large climate ensemble. Climate realizations drive electricity demand; thermal plant availability; and wind, solar, and hydropower generation. Among five initial decarbonization pathways, all exhibit modest to significant resource adequacy failures under climate realizations in 2040, but certain pathways experience significantly less resource adequacy failures at little additional cost relative to other pathways. By identifying and planning for an extreme climate realization that drives the largest resource adequacy failures across our pathways, we produce a new decarbonization pathway that has no resource adequacy failures under any climate realizations. This new pathway is roughly 5% more expensive than other pathways due to greater capacity investment, and shifts investment from wind to solar and natural gas generators. Our analysis suggests modest increases in investment costs can add significant robustness against climate change in decarbonizing power systems. Our framework can help power system planners adapt to climate change by stress testing future plans to potential climate realizations, and offers a unique bridge between energy system and climate modeling.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Introduction: Most hospitalized patients required invasive or non-invasive ventilation and High Flow Nasal Cannula (HFNC). Therefore, this study was conducted to describe the characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) treated by HFNC and its effectiveness for reducing the rate of intubated-mechanical ventilation in the Intensive Care Unit (ICU) of Phu Chanh COVID-19 Department-Binh Duong General Hospital., Methods: It was a cross-sectional and descriptive study. All severe patients with COVID-19 with acute respiratory failure eligible for the study were included. Patient characteristics, clinical symptoms, laboratory results, and treatment methods were collected for analysis; parameters and data related to HFNC treatment and follow-up were analysed., Results: 80 patients, aged of 49.7 ± 16.6 years, were treated with HFNC at admission in ICU. 14 patients had type 2 diabetes (17.5%), 3 patients had chronic respiratory disease (3.8%), 19 patients had high blood pressure (23.8%), and 5 patients with other comorbidities (7.4%). The majority of patients with severe COVID-19 had typical symptoms of COVID-19 such as shortness of breath (97.5%), intensive tired (81.3%), cough (73.7%), anosmia (48.3%), ageusia (41.3%), and fever (26.3%). The results of arterial blood gases demonstrated severe hypoxia under optimal conventional oxygen therapy (PaO 2  = 52.5 ± 17.4 mmHg). Respiratory rate, SpO2, PaO2 were significantly improved after using HFNC at 1st day, 3rd day and 7th day (P < 0.05; P < 0.05; P < 0.01; respectively). Receiver operating characteristics (ROC) index was significantly increased after treating with HFNC vs before HFNC treatment (4.79 ± 1.86, 5.53 ± 2.39, and 7.41 ± 4.24 vs 2.97 ± 0.39; P < 0.05, P < 0.05 and P < 0.01, respectively). 54 (67.5%) patients were success with HFNC treatment and 26 (32.5%) patients with HFNC failure needed to treat with Continuous Positive Airway Pressure (CPAP) (13 patients; 50%) or intubated ventilation (13 patients; 50%)., Conclusion: HFNC therapy could be considered as a useful and effective alternative treatment for patients with acute respiratory failure. HFNC might help to delay the intubated ventilation for patients with respiratory failure and to minimise the risk of invasive ventilation complications and mortality. However, it is crucial to closely monitor the evolution of patient's respiratory status and responsiveness of HFNC treatment to avoid unintended delay of intubation-mechanical ventilation., Trial Registration: An independent ethics committee approved the study (The Ethics Committee of Binh Duong General Hospital; No. HDDD-BVDK BINH DUONG 9.2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice., (© 2024. The Author(s).)

Acquired angioedema with low C1-inhibitor (AAE-C1-INH) is a rare disorder characterized by an acquired deficiency in the C1 esterase inhibitor (C1-INH). This case report describes a 79-year-old patient presenting to the emergency department for painless swelling of his scrotum, penile shaft, and left lower and upper extremities with lab values consistent with acquired angioedema without identifiable lymphoreticular or rheumatic disorder on history, exam, or total body PET scan. Proper diagnosis of AAE-C1-INH is essential to prevent life-threatening airway compromise, ensure proper therapy, and exclude lymphoreticular disorders as the etiology of AAE-C1-INH., Competing Interests: The authors other than Dr Timothy Craig have no conflicts of interest to declare. Dr Timothy Craig's conflicts are research conflicts with BioMarin, Kalvista, Pharvaris, CSL Behring, Takeda, Ionis, Intellia, Astria, and Grifols; speaking conflicts for Takeda, CSL Behring, and Grifols; and consultant conflicts for BioMarin, Intellia, CSL Behring, Takeda, BioMarin, Ionis, Astria, Kalvista, CSL Behring, and Biocryst. He also has center designations from the International Hereditary Angioedema Association and Alpha-1 Foundation and is a member of the Medical Advisory Board for the HAE-A., (Copyright © 2024 Meghan V. Matheny et al.)

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life-threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on-demand treatment in all patients and the prevention of attacks (short-term prophylaxis [STP] and long-term prophylaxis [LTP]) in appropriate patients. All approved on-demand and most LTP medications require subcutaneous or intravenous administration. Injection-related challenges include trypanophobia (fear of needles), difficulty with self-administration, injection-site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety-all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers., Aim: To review oral therapies, approved or in development, for on-demand treatment and/or prevention of HAE attacks., Materials and Methods: To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024)., Results: Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on-demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on-demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE-4666, and VE-4062) are in early development for LTP., Conclusion: Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Competing Interests: MB has conducted paid consulting work for Medtronic, Phytome life sciences, Canopy, Esteve and is deputy medical director of Medefer. TC and AN declare no conflicts of interest.

Background: Lanadelumab was well tolerated and effective in preventing hereditary angioedema (HAE) attacks in the phase 3, double-blind, placebo-controlled Hereditary angioEdema Long-term Prophylaxis (HELP) study and subsequent HELP open-label extension (OLE) study (NCT02741596)., Objective: To evaluate outcomes from HELP OLE for adolescent patients aged 12 to 17 years., Methods: The HELP OLE study comprised patients who completed the HELP study (rollovers) and new eligible (lanadelumab-naive) patients. Rollovers received a single dose of lanadelumab 300 mg at the last HELP study visit (day 0). Treatment was then paused until patients experienced their first investigator-confirmed HAE attack, after which lanadelumab 300 mg was administered every 2 weeks for up to 33 months (4 wk/mo). Lanadelumab-naive patients received lanadelumab 300 mg every 2 weeks from day 0. Patient-reported outcomes included Angioedema Quality of Life Questionnaire. Safety was monitored throughout the study., Results: The subgroup analysis included 21 patients (8 rollovers and 13 lanadelumab-naive patients); 95.2% completed at least 30 months in the study. The mean (SD) monthly attack rate decreased from 1.58 (1.0) at baseline to 0.11 (0.2) during treatment (mean, 94.7% reduction). A total of 8 (38.1%) patients were attack-free during treatment and, on average, 99.1% of days were attack-free (mean, 27.7 d/mo). Patients reported a mean (SD) Angioedema Quality of Life Questionnaire total score of 27.5 (17.5) at baseline vs 7.5 (13.2) at the end of the study. There were 12 (57.1%) patients who reported treatment-related treatment-emergent adverse events; however, there were no treatment-related serious adverse events., Conclusion: Lanadelumab provided long-term efficacy in preventing HAE attacks, was associated with clinically meaningful improvements in health-related quality of life and high levels of treatment satisfaction, and was well tolerated in adolescent patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02741596., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment., Objective: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE)., Methods: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022)., Results: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms., Conclusion: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care., (Copyright © 2024. Published by Elsevier Inc.)

Background: Syphilis epidemics among women and men-who-have-sex-with-men (MSM) may be connected, but these connections are poorly understood. Using egocentric network data from a U.S. urban MSM cohort, we examined socio-demographics, behaviors, and syphilis positivity among MSM with (1) direct (MSM who report sex with women, MSMW); (2) indirect (MSM who only report male partners, some of whom are MSMW, MSMO/W); and (3) no (MSM who only report male partners and whose partners only have sex with men, MSMO/O) connection to women., Methods: Sexually-active MSM aged 18-45 years were administered behavioral and network interviews (recall period: three months) and syphilis/HIV testing. Syphilis positivity was defined as RPR titer >1:8. Modified Poisson regression was used to test for differences across groups., Results: Among 385 MSM, 14.5% were MSMW and 22.3% were MSMO/W. MSMW and MSMO/W were significantly more likely than MSMO/O to report sex behaviors associated with increased syphilis acquisition/transmission risk, including: > 2 sex partners [MSMW aPR:1.28 (0.98-1.68); MSMO/W aPR:1.35 (1.09-1.69)], concurrent sex partners [MSMW aPR:1.50 (1.17-1.92); MSMO/W aPR:1.39 (1.11-1.74)], and for MSMW only, transactional sex [aPR:2.07 (1.11-3.88)]. Syphilis positivity was 16.4% and was lower among MSMW (9.4%) and MSMO/W (14.1%) than MSMO/O (18.5%), but differences were not significant., Conclusions: There may be considerable connectivity between MSM and female sex partners that could facilitate syphilis transmission, and behaviors that increase acquisition/transmission risk among MSMW and MSMO/W may be distinct from MSMO/O. Future work should focus on examining the context and temporal patterns of sex partnerships among MSMW and MSMO/W., Competing Interests: Conflicts of Interest and Sources of Support: This work was supported by the Centers for Disease Control and Prevention [1U01PS005171-01], and the Johns Hopkins University Center for AIDS Research [P30AI094189]., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Hereditary angioedema is a rare disorder characterized by episodic, potentially life-threatening swelling caused by kallikrein-kinin dysregulation. Long-term prophylaxis can stabilize this system. Donidalorsen, an antisense oligonucleotide, specifically reduces prekallikrein expression., Methods: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary angioedema to receive donidalorsen (80 mg subcutaneously) or placebo once every 4 or 8 weeks. The primary end point was the time-normalized number of investigator-confirmed hereditary angioedema attacks per 4 weeks (attack rate) from week 1 to week 25., Results: A total of 90 patients received donidalorsen every 4 weeks (45 patients), donidalorsen every 8 weeks (23 patients), or placebo (22 patients). The least-squares mean time-normalized attack rate was 0.44 (95% CI, 0.27 to 0.73) in the 4-week group, 1.02 (95% CI, 0.65 to 1.59) in the 8-week group, and 2.26 (95% CI, 1.66 to 3.09) in the placebo group. The mean attack rate from week 1 to week 25 was 81% lower (95% CI, 65 to 89) in the 4-week group than in the placebo group (P<0.001) and 55% lower (95% CI, 22 to 74) in the 8-week group than in the placebo group (P = 0.004); the median reduction in the attack rate from baseline was 90% in the 4-week group, 83% in the 8-week group, and 16% in the placebo group. The mean attack rate during weeks 5 to 25 was 87% lower (95% CI, 72 to 94) in the 4-week group than in the placebo group (P<0.001) and 60% lower (95% CI, 25 to 79) in the 8-week group than in the placebo group. Donidalorsen administered every 4 weeks resulted in an improvement in the least-squares mean total score for the change at week 25 on the Angioedema Quality-of-Life Questionnaire (scores range from 0 to 100, with a score of 100 indicating the worst possible quality of life) that was 18.6 points (95% CI, 9.5 to 27.7) better than that with placebo (P<0.001). The most common adverse events were erythema at the injection site, headache, and nasopharyngitis; 98% of adverse events were mild or moderate in severity., Conclusions: Donidalorsen treatment reduced the hereditary angioedema attack rate, a finding that supports potential prophylactic use for hereditary angioedema. (Funded by Ionis Pharmaceuticals; OASIS-HAE ClinicalTrials.gov number, NCT05139810.)., (Copyright © 2024 Massachusetts Medical Society.)

Hereditary angioedema is a rare autosomal dominant condition characterized by episodes of swelling of the upper airway, intestines, and skin. The disorder is characterized by deficiency in C1 esterase inhibitor (C1-INH) or a decrease in functional C1-INH. Treatment options include on demand therapy (treatment of acute attacks), long-term prophylaxis, and short-term prophylaxis. Corticosteroids, epinephrine, and antihistamines are not effective for this form of angioedema. The high mortality in patients undiagnosed underscores a need for broader physician awareness to identify these patients and initiate therapy., Competing Interests: Disclosure Dr T. Craig declares the following conflicts of interest: Research—CSL Behring, Ionis, Biocryst, Takeda, Pharvaris, BioMarin, Kalvista. Speaker—Grifols, Takeda, CSL Behring. Consultant—BioMarin, CSL Behring, Takeda, Biocryst, Spark. Drs A. Sarkar and C. Nwagwu have no conflicts to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Postoperative prostate radiotherapy requires large planning target volume (PTV) margins to account for motion and deformation of the prostate bed. Adaptive radiation therapy (ART) can incorporate image-guidance data to personalize PTVs that maintain coverage while reducing toxicity. We present feasibility and dosimetry results of a prospective study of postprostatectomy ART. Twenty-one patients were treated with single-adaptation ART. Conventional treatments were delivered for fractions 1 to 6 and adapted plans for the remaining 27 fractions. Clinical target volumes (CTVs) and small bowel delineated on fraction 1 to 4 CBCT were used to generate adapted PTVs and planning organ-at-risk (OAR) volumes for adapted plans. PTV volume and OAR dose were compared between ART and conventional using Wilcoxon signed-rank tests. Weekly CBCT were used to assess the fraction of CTV covered by PTV, CTV D99, and small bowel D 1cc . Clinical metrics were compared using a Student's t-test (p < 0.05 significant). Offline adaptive planning required 1.9 ± 0.4 days (mean ± SD). ART decreased mean adapted PTV volume 61 ± 37 cc and bladder wall D50 compared with conventional treatment (p < 0.01). The CTV was fully covered for 96% (97%) of fractions with ART (conventional). Reconstructing dose on weekly CBCT, a nonsignificant reduction in CTV D99 was observed with ART (94%) compared to conventional (96%). Reduced CTV D99 with ART was significantly correlated with large anterior-posterior rectal diameter on simulation CT. ART reduced the number of fractions exceeding our institution's small bowel D1c limit from 14% to 7%. This study has demonstrated the feasibility of offline ART for post-prostatectomy cancer. ART facilitates PTV volume reduction while maintaining reasonable CTV coverage and can reduce the dose to adjacent normal tissues., Competing Interests: Conflicts of Interest Charles Catton is a member of the advisory board for Abbvie Corp. Sandra Meyers has received honoraria and grant funding from Varian Medical Systems, unrelated to this work. No other conflicts of interest exist for any of the authors., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary angioedema (HAE) is an autosomal dominant disease with variable expression. In some families with identical genetic abnormalities, the expression can range from several attacks per month to no attacks at all. It is hypothesized that post-transcriptional gene regulation accounts for the variable expression of the disease., Objective: To identify candidate microRNAs (miRNAs) that could play a role in HAE by determining whether miRNAs are differentially expressed in patients with HAE vs non-HAE individuals and whether expression profiles are tracked with severity., Methods: This study compared serum miRNA expression in patients with HAE vs non-HAE using RNA sequencing. Associations between miRNA expression and HAE severity were assessed in patients with mild disease (<6 attacks a year) vs severe disease (>1 attack per month). The functions of candidate miRNAs were analyzed using in silico methods., Results: There were robust miRNA expression differences between patients with HAE and non-HAE controls. A cluster analysis identified subgroups of patients with HAE having unique miRNA profiles that tracked with frequency of attacks. Two miRNAs, miR-99b-5p and miR-127-3p, were differentially expressed between mild and severe HAE (adjusted P < .05). In silico analysis revealed a function of differentially expressed miRNAs in regulation of C1 esterase inhibitor, kininogen, the bradykinin B2 receptor, and adherens junction function., Conclusion: Candidate microRNAs were identified that could distinguish patients with and without HAE and may be used to identify phenotypes of HAE., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants., Objective: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks., Methods: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internet-based survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9-point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2., Results: A total of 58 worldwide panelists completed both rounds. The first round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of five key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction., Conclusions: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of five key outcomes., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

The efficiency of a catalytic process is assessed based on conversion, yield, and time effectiveness. However, these parameters are insufficient for evaluating environmentally sustainable research. As the world is urged to shift towards green catalysis, additional factors such as reaction media, raw material availability, sustainability, waste minimization and catalyst biosafety, need to be considered to accurately determine the efficacy and sustainability of the process. By combining the high porosity and versatility of metal organic frameworks (MOFs) and the activity of gold nanoparticles (AuNPs), efficient, cyclable and biosafe composite catalysts can be achieved. Thus, a composite based on AuNPs and the nanometric flexible porous iron(III) aminoterephthalate MIL-88B-NH 2 was successfully synthesized and fully characterized. This nanocomposite was tested as catalyst in the reduction of nitroarenes, which were identified as anthropogenic water pollutants, reaching cyclable high conversion rates at short times for different nitroarenes. Both synthesis and catalytic reactions were performed using green conditions, and even further tested in a time-optimizing one-pot synthesis and catalysis experiment. The sustainability and environmental impact of the catalytic conditions were assessed by green metrics. Thus, this study provides an easily implementable synthesis, and efficient catalysis, while minimizing the environmental and health impact of the process., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Purpose: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy., Methods and Materials: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores., Results: The mean dose and dose to 40% of the brain (D40) were 2.7 and 4.1 Gy less among proton-treated patients compared with photon-treated patients (P = .03 and .007, respectively). Mean doses to the left and right hippocampi were 11.2 Gy lower among proton-treated patients (P < .001 for both). Mean doses to the left and right temporal lobes were 6.9 and 7.1 Gy lower with proton treatment, respectively (P < .001 for both). Models of cognition found statistically significant associations between higher mean brain dose and reduced verbal comprehension, increased right temporal lobe D40 with reduced perceptual reasoning, and greater left temporal mean dose with reduced working memory. Higher brain D40 was associated with reduced processing speed and global IQ scores., Conclusions: Proton therapy reduces doses to normal brain structures compared with photon treatment. This leads to reduced cognitive decline after radiation therapy across multiple intellectual endpoints. Proton therapy should be offered to children receiving radiation for medulloblastoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Care home residents often experience polypharmacy (defined as taking five or more regular medicines). Therefore, we need to ensure that residents only take the medications that are appropriate or provide value (also known as medicines optimisation). To achieve this, deprescribing, or the reduction or stopping of prescription medicines that may no longer be providing benefit, can help manage polypharmacy and improve outcomes. Various tools, guides, and approaches have been developed to help support health professionals to deprescribe in regular practice. Little evaluation of these tools has been conducted and no work has been done in the care home setting., Objective: This qualitative study aimed to assess distinct types of deprescribing tools for acceptability, feasibility, and suitability for the care home setting., Methods: Cognitive (think-aloud) interviews with care home staff in England were conducted (from December 2021 to June 2022) to assess five different deprescribing tools. The tools included a general deprescribing guidance, a generic (non-drug specific) deprescribing framework, a drug-specific deprescribing guideline/guide, a tool for identifying potentially inappropriate medications, and an electronic clinical decision support tool. Participants were recruited via their participation in another deprescribing study. The Consolidated Framework for Implementation Research informed the data collection and analysis., Results: Eight care home staff from 7 different care homes were interviewed. The five deprescribing tools were reviewed and assessed as not acceptable, feasible, or suitable for the care home setting. All would require significant modifications for use in the care home setting (e.g., language, design, and its function or use with different stakeholders)., Conclusions: As none of the tools were deemed acceptable, feasible, and suitable, future work is warranted to develop and tailor deprescribing tools for the care home setting, considering its specific context and users. Deprescribing implemented safely and successfully in care homes can benefit residents and the wider health economy., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2023. Published by Elsevier Inc.)

Background: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients 12 years or older., Objective: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat., Methods: APeX-2 was a phase 3, parallel-group, multicenter trial in patients with HAE caused by C1-inhibitor deficiency (NCT03485911). Part 1 was a randomized, double-blind, placebo-controlled evaluation of 150 and 110 mg of berotralstat over 24 weeks. In part 2, berotralstat-treated patients continued the same treatment, and placebo-treated patients were re-randomized to 150 or 110 mg of berotralstat for 24 weeks. In part 3, all patients were treated with open-label berotralstat at 150 mg, which could be continued for up to an additional 4 years. In part 3, the primary endpoint was long-term safety and tolerability. Secondary endpoints included HAE attack rates and quality of life (QoL)., Results: Eighty-one patients entered part 3. Treatment-emergent adverse events (TEAEs) occurred in 82.7% of patients, with most being mild or moderate in severity. The most common TEAEs were nasopharyngitis, urinary tract infection, abdominal pain, arthralgia, coronavirus infection, and diarrhea. Drug-related TEAEs occurred in 14.8% of patients, but none were serious. For patients who completed 96 weeks of berotralstat treatment (n = 70), the mean (standard error) change in attack rate from baseline was -2.21 (0.20) attacks/mo. Clinically meaningful improvements in QoL were also observed, with the largest improvements in the functioning domain., Conclusion: Berotralstat was generally well tolerated, provided rapid and sustained reductions in HAE attacks and improved QoL over 96 weeks., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent innovations in image guidance, treatment delivery, and adaptive radiotherapy (RT) have created a new paradigm for planning target volume (PTV) margin design for patients with prostate cancer. We performed a review of the recent literature on PTV margin selection and design for intact prostate RT, excluding post-operative RT, brachytherapy, and proton therapy. Our review describes the increased focus on prostate and seminal vesicles as heterogenous deforming structures with further emergence of intra-prostatic GTV boost and concurrent pelvic lymph node treatment. To capture recent innovations, we highlight the evolution in cone beam CT guidance, and increasing use of MRI for improved target delineation and image registration and supporting online adaptive RT. Moreover, we summarize new and evolving image-guidance treatment platforms as well as recent reports of novel immobilization strategies and motion tracking. Our report also captures recent implementations of artificial intelligence to support image guidance and adaptive RT. To characterize the clinical impact of PTV margin changes via model-based risk estimates and clinical trials, we highlight recent high impact reports. Our report focusses on topics in the context of PTV margins but also showcase studies attempting to move beyond the PTV margin recipes with robust optimization and probabilistic planning approaches. Although guidelines exist for target margins conventional using CT-based image guidance, further validation is required to understand the optimal margins for online adaptation either alone or combined with real-time motion compensation to minimize systematic and random uncertainties in the treatment of patients with prostate cancer., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Chronic spontaneous urticaria (CSU) is a common condition treated by allergist/immunologists, but the only FDA-approved biologic medication, omalizumab, may be underutilized globally., Objective: This study was performed to determine the global prescription of omalizumab for treatment of CSU by allergists/immunologists., Methods: Anonymous questionnaire surveys were distributed online to World Allergy Organization (WAO) members worldwide. Categorical data were analyzed for descriptive analysis using one-way frequency tabulation in SAS 9.4., Results: There were 348 respondents (43 missing data); Average age 51 (range 28-90); M/F 48%/52%. 58% had > 15 years of clinical experience and 10% < 5; 42% worked in private clinics, 36% public hospitals, 24% academia, 18% private hospitals, and 4% in community practice. Eighty-two percent (82%) prescribed omalizumab for CSU patients and use of omalizumab was highest among young practitioners. The most significant barriers were cost (63%) and restricted formulary (24%). Drug safety (63%) and chances of adverse events (47%) were the most significant factors deciding treatment. Twenty-two percent (22%) reported 80-100% of CSU patients were complete responders to omalizumab; 34% preferred increasing frequency (q 2-weeks), and 18% preferred increasing dose (600 mg q 4-weeks) for partial or non-responders. UAS7, UCT, and CU-QoL were used to assess CSU by 55%, 29%, and 25% of respondents, respectively. Autoimmune thyroid disease (62%), thyroid abnormality (43%) and allergic rhinitis (35%) were the most frequent comorbidities reported., Conclusions: Most clinicians favored omalizumab over other potential treatments due to safety. Although younger clinicians were more likely to prescribe omalizumab, cost and formulary access were major barriers. Only 22% of respondents reported 80% or greater of their patients had complete response to omalizumab, indicating the need for novel CSU therapies., (© 2023 The Authors.)

Background: Hereditary angioedema (HAE) is a rare condition characterized by potentially fatal, recurrent episodes of painful swelling. Whereas there are limited studies evaluating the quality of life of individuals with HAE, none have evaluated the impact of HAE on older adults., Objective: To evaluate the effect of HAE on older adults through qualitative methodology., Methods: A group of 3 physicians with extensive research and clinical experience in HAE developed a focus group guidebook highlighting issues of importance to older adults. A total of 17 patients with HAE (type I or II) aged 60 years and older participated in focus groups. Three independent reviewers coded each focus group transcript using a thematic saturation approach., Results: Reviewers identified 7 core themes from the focus groups. The themes identified encompassed the following: (1) challenges with securing medications and insurance concerns; (2) the experience of living with HAE before the advent of newer and more effective therapeutic options; (3) a worsening of HAE attack frequency and severity with aging; (4) the effects of comorbid conditions such as arthritis, memory loss, and irritable bowel syndrome; (5) changes in HAE with menopause; and (6) changing perspective on HAE with age, the effect of HAE on interpersonal relationships including the decision to have children, and goals for future care and research including support groups and a desire to be included in clinical trials., Conclusion: Older adults with HAE have specific challenges and concerns that may be unique compared with younger populations. Health care providers should address these to provide optimal care., Competing Interests: Disclosures Dr Baptist reports receiving research and consulting support from BioCryst and Takeda. Dr Craig reports research conflicts with BioMarin, Kalvista, Pharvaris, GlaxoSmithKline, CSL Behring, Takeda, Ionis, Intellia, AstraZeneca, Pfizer, Regeneron, and Grifols; speaking conflicts with Takeda, CSL Behring, and Grifols; is a consultant for BioMarin, Intellia, CSL Behring, Takeda, BioMarin, Ionis, AstraZeneca, Kalvista, CSL Behring, and BioCryst; has center designations from the International Hereditary Angioedema Association and Alpha-1 (HAE-A) Foundation; and is a member of the medical advisory board for the HAE-A. Dr Riedl reports receiving research support from BioCryst, BioMarin, CSL Behring, Ionis, Kalvista, Pharvaris, and Takeda; consulting fees from Astria, BioCryst, BioMarin, CSL Behring, Cycle, Intellia, Kalvista, Ono Pharma, Pharming, Pharvaris, and Takeda; honoraria for speaker presentations from CSL Behring, Pharming, and Takeda; and is a member of the US HAE-A medical advisory board. The other authors have no conflicts of interest to report., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)