Search

Conventionally, patients who do not experience a biochemical recurrence (BCR) within 5 years of radiotherapy (RT) for non-metastatic prostate cancer (PCa) are considered cured. However, the natural history of disease after this landmark time remains poorly understood. Similarly, the natural history following BCR within five years of RT remains unexplored. We performed a pooled analysis of men enrolled in 21 randomized controlled trials with long-term follow-up to determine incidence of subsequent cancer-specific events including distant metastasis (DM) and prostate cancer-specific mortality (PCSM) in both groups. Individual patient data were obtained from the MARCAP consortium. Cumulative incidence of DM was estimated using competing risk methods considering any deaths as competing events. Competing risk regression (for DM and PCa-specific mortality [PCSM]) were applied to determine the association between treatment strategy (e.g., escalating RT dose with or without androgen deprivation therapy) with DM and PCSM after adjustment for time to BCR, tumor stage, Gleason score, age at treatment, and baseline PSA. Time of randomization was used to define the intervals to events of interest. Overall, of the 13,468 eligible patients across 21 trials, 3,902 experienced a BCR event within 5 years (median follow-up = 137 months, interquartile range [IQR] = 135 – 139). Among patients who did not experience any BCR by 5 years (n = 9,566), median follow-up was 129 (IQR = 128 – 130) months. The estimated 10-year cumulative incidence rates (95% CI) of DM and PCSM were 3.3% (2.9–3.7) and 1.2% (1.0–1.4), respectively. On competing risk regression, we did not find sufficient evidence to reject the null hypothesis of no association of upfront treatment with relative incidence of post-BCR DM and PCSM. Among patients who experienced a BCR within five years of RT, 10-year rates of DM and PCSM were 39.3% (37.7–40.8) and 29.0% (27.5–30.5), respectively. Among PCa patients treated with RT those who do not experience a BCR event by 5 years, the overall 10-year rates of DM and PCSM are approximately 3% and 1%, consistent with a curative state. However, for patients with BCR within 5 years, 10-year DM and PCSM rates approach 40% and 30%, consistent with aggressive disease. Further work will help refine the definition of "cure" following RT. [ABSTRACT FROM AUTHOR]

Pre-clinical studies suggest that prior LT could portend neuroendocrine differentiation and could result in compromised response to subsequent lines of systemic therapy including androgen deprivation therapy (ADT) or androgen receptor pathway inhibitors (ARPI). In contrary, clinical studies show conflicting findings in this domain. Our analysis further explores whether prior local therapy plays a modifying role on the first line treatment effect on OS. Additionally, we investigate whether prior local therapy have an independent association with OS and radiographic progression free survival in this cohort. We performed an individual patient data based meta-analysis of COU-AA-302 and ACIS trials that included men with chemotherapy naïve mCRPC. In the first trial, patients were randomly assigned to ADT versus ADT plus abiraterone (ADT+AA-P) while in the second one, patients were randomly assigned to ADT+AA-P versus ADT plus apalutamide plus AA-P (APA + AA-P). We applied a hierarchical multivariable Bayesian Cox proportional hazard regression model to determine if there was any difference in treatment effect on overall survival (OS) among patients stratified by prior LT. Further, we determined the independent association of exposure to prior LT with radiographic progression-free survival (rPFS) and OS in the entire study cohort. Overall, 2032 patients (n=527 in ADT group; n=1020 in ADT+AA-P group; n=485 to APA+AA-P) were included in this study; of whom, 339 in the ADT group, 559 in the AA-P group, and 234 in the APA+AA-P group had prior LT. Among patients with prior LT, 253 had radical prostatectomy (RP) alone, 345 had RP plus radiotherapy (RT), and 534 had RT alone, respectively. Relative to ADT+AA-P, we found no difference in treatment effect on OS from ADT alone (hazard ratio [HR] for the interaction term: 0.90; 95% credible interval [CrI]: 0.69-1.17) or APA+AA-P (HR for the interaction term: 1.29 [0.99-1.69]), among patients with and without prior LT. We did not find any significant association of LT modality with rPFS (HR for RP: 0.98 [0.81-1.18]; HR for RT: 0.99 [0.86-1.16]; and HR for RP+RT: 1.03 [0.86-1.23]) and OS (HR for RP: 0.84 [0.69-1.02]; HR for RT: 1.03 [0.89-1.19]; and HR for RP+RT: 0.88 [0.73-1.05]) in the overall study cohort. In this meta-analysis, we did not find any significantly compromised treatment effects from first line ARPI in patients who received prior LT. Further, there was no significant association of prior LT modality with risk of radiographic progression or deaths, respectively. [ABSTRACT FROM AUTHOR]

Both acute and late toxicity after prostate radiotherapy arise from normal tissue irradiation at the time of treatment. The association between acute toxicity and late toxicity remains poorly understood. We sought to characterize the relationship between acute and late genitourinary (GU) and gastrointestinal (GI) toxicity, both as scored by physicians and as reported by patients, among patients receiving radiotherapy for prostate cancer. Individual patient data for trials that had acute and late GU and GI toxicity data were extracted from the MARCAP consortium. Physician-reported acute (≤3 months from treatment) and late (>3 months from treatment) GU and GI toxicity were graded using Radiation Therapy Oncology Group criteria or Common Terminology Criteria. Urinary and bowel patient-reported quality of life (QOL) data from Expanded Prostate Cancer Index Composite (EPIC) questionnaires were used to identify late QOL decrements greater than twice the minimal clinically important difference (>2x MCID) at any time beyond 3 months post-treatment. MCID was defined as half of the standard deviation at baseline. Generalized linear mixed models were used to examine the relationship between acute grade ≥2 GU and GI toxicity and both late grade ≥2 GU and GI toxicity and late decrement >2x MCID in urinary and bowel QOL. These were adjusted for age, performance status, receipt of androgen deprivation therapy (ADT), use of intensity modulated radiotherapy (IMRT), and use of moderate hypofractionation. 6,349 patients from seven trials were included (conventional fractionation: n = 4,128; moderate hypofractionation: n = 2,221). Median follow-up was 76 months (interquartile range [IQR], 59-101 months). 71.3% received IMRT. Median equivalent dose (EQD2) was 74 Gy (IQR, 72-76 Gy). 51.8% received ADT. Rates of acute grade ≥2 GU and GI toxicity were 29.6% and 14.9%, respectively. Rates of late grade ≥2 GU and GI toxicity were 15.7% and 15.2%, respectively, while rates of urinary and bowel QOL decrement >2x MCID were 19% and 33%, respectively. Acute grade ≥2 GU toxicity was associated with late grade ≥2 GU toxicity (odds ratio [OR] 2.09, P <0.001), and acute grade ≥2 GI toxicity was associated with late grade ≥2 GI toxicity (OR 2.94, P <0.001). Similarly, acute grade ≥2 GU toxicity was associated with late urinary QOL decrement >2x MCID (OR 1.46, P = 0.02), and acute grade ≥2 GI toxicity was associated with late bowel QOL decrement >2x MCID (OR 2.00, P <0.001). Acute toxicity following conventionally fractionated or moderately hypofractionated prostate radiotherapy was significantly associated with late GU and GI toxicity as defined both by physician scoring and patient-reported QOL metrics. These data suggest that efforts to prevent acute toxicity may translate into reduced risks of late toxicity. [ABSTRACT FROM AUTHOR]

Background/objective: Slowing the progression of diabetic kidney disease (DKD) is critical. We conducted a randomized controlled trial to target risk factors for DKD progression., Methods: We evaluated the effect of a pharmacist-led intervention focused on supporting healthy behaviors, medication management, and self-monitoring on decline in estimated glomerular filtration rate (eGFR) for 36 months compared with an educational control., Results: We randomized 138 individuals to the intervention group and 143 to control. At baseline, mean (SD) eGFR was 80.7 (21.7) mL/min/1.73m 2 , 56% of participants had chronic kidney disease and a history of uncontrolled hypertension with a baseline SBP of 134.3 mm Hg. The mean (SD) decline in eGFR by cystatin C from baseline to 36 months was 5.0 (19.6) and 5.9 (18.6) mL/min/1.73m 2 for the control and intervention groups, respectively, with no significant between-group difference ( P =0.75)., Conclusions: We did not observe a significant difference in clinical outcomes by study arm. However, we showed that individuals with DKD will engage in a pharmacist-led intervention. The potential explanations for a lack of change in DKD risk factors can be attributed to 5 broad issues, challenges: (1) associated with enrolling patients with low eGFR and poor BP control; (2) implementing the intervention; (3) limited duration during which to observe any clinical benefit from the intervention; (4) potential co-intervention or contamination; and (5) low statistical power., Competing Interests: This study was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (1R01DK93938.). H.B. reports research grants from the PhRMA Foundation, Proteus Digital Health, Otsuka, Novo Nordisk, Sanofi, and Improved Patient Outcomes, as well as consulting from Sanofi, Novartis, Otsuka, Abbott, Preventric Diagnostics, and the Medicines Company. U.D.P. was supported by R01DK093938, R34DK102166, and P30DK096493 before joining Gilead Sciences in 2016. C.A.D. was partially supported by UL1TR002553, the NIH Clinical and Translational Science Award at Duke. J.P. was partially supported by P30AG02871615, the NIA Claude D. Pepper Older Americans Independence Center Award at Duke. H.B. was partially supported by U24-HL137907 and U24-DK065176. A.A.L. reports receiving funds from Otsuka and PhRMA Foundation, and is supported by VA HSR&D grant #18-234. M.J.C. reports funding from the National Institutes of Health (1R01NR019594-01), the Veterans Affairs Quality Enhancement Research Initiative (VA QUE 20-012), and the Veterans Affairs Office of Rural Health. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Anxiety is a common co-occurring condition for autistic preschoolers. Whilst there has been extensive research evaluating anxiety prevention/reduction interventions for neurotypical preschoolers, such research is limited for autistic children. Fifty-seven parents of autistic 4-5-year olds, with varying levels of anxiety, participated in a randomised controlled trial of an autism-specific, parent-mediated intervention (CLK-CUES) to prevent or reduce anxiety in autistic preschoolers. Baseline, short-term (post-intervention) and longer term (12 months follow-up) assessments included child anxiety (ASC-ASD-P and PAS-R), intolerance of uncertainty, and parent well-being. (Trial registration ACTRN12620001322921). There were no reports of harmful effects of the intervention or trial. Linear mixed models show a significant group x time interaction for ASC-ASD-P Total score and the Uncertainty subscale with medium and large effect sizes. Post-hoc analyses show a significant decline for only the intervention group in anxiety (specifically, anxiety around uncertainty) from pre-post intervention, maintained at one year follow-up. There was no change on the PAS-R or other ASC-ASD-P subscales. CLK-CUES shows promise as a way to prevent and reduce anxiety in young autistic children, specifically anxiety related to uncertainty. Trials with larger samples are warranted. Findings also highlight the importance of using measures designed for autistic children., (© 2024. The Author(s).)

Background and Objective: Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists varies widely. We evaluate TR kinetics and the oncological impact of an effective castration period in patients receiving definitive radiotherapy and ADT for prostate cancer., Methods: We obtained individual patient data from randomized controlled trials of radiotherapy with ADT and prospectively collected serial testosterone data from the MARCAP Consortium. We estimated the times to noncastrate TR (>1.7 nmol/l) and nonhypogonadal TR (>8.0 nmol/l) were estimated for each prescribed ADT duration, and developed corresponding nomograms. The association between effective castration period and metastasis-free survival (MFS) for any given ADT duration was evaluated via multivariable Cox regression. We conducted cubic spline analyses to assess nonlinear associations., Key Findings and Limitations: We included 1444 men from five trials in the analysis, of whom 115 received 4 mo, 880 received 6 mo, 353 received 18 mo, 36 received 28 mo, and 60 received 36 mo of ADT. Times to noncastrate TR and to nonhypogonadal TR varied considerably by ADT duration. Higher baseline testosterone and lower age were associated with a higher likelihood of TR (p < 0.001 for both). Effective castration period was not linearly associated with MFS for any ADT duration on Cox regression. Cubic spline analysis revealed that the optimal effective castration period for an MFS benefit was 10.6 mo for men who received 6 mo of ADT and 18 mo for men who received 18 mo of ADT., Conclusions and Clinical Implications: Time to TR varies according to the ADT duration, baseline testosterone, and age. The relationship between effective castration period and MFS may be nonlinear, with a longer effective castration period being helpful for men receiving 6 mo of ADT., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Penium margaritaceum, a unicellular zygnematophyte (Streptophyta), was employed to elucidate changes in cell expansion when cells were challenged with the fungal pectinolytic enzyme, pectate lyase, and/or the microtubule disrupting agent, amiprophos-methyl (APM). Microtubule disruption by APM results in significant swelling at expansion zones. These swollen zones provide an easy marker for the location of expansion zones, particularly in cells with altered cell wall pectin. Short term treatment with pectate lyase shows pectin degradation primarily at the isthmus expansion zone and two satellite bands, corresponding with the location of future expansion in daughter cells. When the homogalacturonan lattice of the cell wall is removed by treatment with pectate lyase during long treatments, cell division is maintained, but daughter cell products are considerably smaller. Treatment of cells with a mixture of both pectate lyase and APM results in a distinct phenotype, consisting of "dumbbell"-shaped cells, as APM-induced swelling occurs at the novel expansion centers exposed by pectate lyase treatment. These cells also possess other curious alterations including an extensive, chloroplast-free cytoplasmic zone at the center of the cell, a septum containing ß-glycan, arabinogalactan and homogalacturonan epitopes, unique stacks of ER, displaced Golgi bodies and an extensive network of vacuoles. These results provide insight into the importance of cell wall integrity in defining the location of cell growth and division in P. margaritaceum. Understanding these processes in a unicellular zygnematophyte may provide insights into steps involved in the evolution of land plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: This study aimed to compare acceleration and deceleration demands of intercounty Camogie players, and differences across playing positions and halves of play., Hypothesis: The middle 3 positions will have greatest accelerations and decelerations variables across match play and halves of play., Study Design: Nonrandomized, repeated measures design., Level of Evidence: Level 4., Methods: Global positioning systems (GPS) (10 Hz) collected data from 28 participants during 18 competitive matches across 2 seasons; 206 individual player datasets were analyzed., Results: Half-backs ( P < 0.05; effect size [ES], -1.75) and midfielders ( P < 0.05; ES, -1.68) covered significantly greater total number of accelerations than full-forwards. In acceleration zone 4, midfielders ( P < 0.05; ES, = -1.67) and half forwards covered a significantly greater number than full-forwards ( P < 0.01; ES, = -1.41). Midfielders accumulated a significantly greater distance in acceleration zone 4 than full-backs ( P < 0.05; ES, = -0.57). Significant decrements were observed between halves in total number of accelerations ( P < 0.01; ES, = 0.49), accelerations in zones 1 to 4 ( P < 0.01; ES, 0.16-0.43), total distance of accelerations, and acceleration distance in zones 2 to 4 ( P < 0.05; ES, 0.25; P < 0.01; ES, 0.45; P < 0.01; ES, 0.38). There were significant decrements in the total number of decelerations ( P < 0.01; ES, 0.43), number of decelerations in zones 2 ( P < 0.05; ES, 0.25), 3 ( P < 0.01; ES, 0.45), and 4 ( P < 0.01; ES, 0.38), and total deceleration distance ( P < 0.01; ES, 0.16)., Conclusion: Half-backs and midfielders covered significantly greater total number of accelerations than full-forwards. Significant decrements in several acceleration and deceleration variables were observed between halves., Clinical Relevance: Players competing in intercounty Camogie should receive progressive exposure to acceleration and deceleration-based movement demands to prepare players for intercounty Camogie match play., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Abstract: Duggan, JD, Byrne, P, Malone, S, Cooper, S-M, and Moody, J. The physical and physiological demands of intercounty camogie during competitive match-play. J Strength Cond Res 38(9): e510-e520, 2024-The aim of this study was to determine the physical and physiological demands of intercounty camogie match-play between positions and halves of play. Data were collected from 28 players during 18 competitive games using global positioning systems (10-Hz) and heart rate monitors (2.4-GHz). The study demonstrated that intercounty camogie players covered a total distance (TD) (m ± SD) of 6,040 ± 628 m, relative distance (RD) of 83 ± 13 m·min-1, and maximum speed of 25 ± 1 km·h-1. Furthermore, the players covered a mean sprint distance of 214 ± 112 m and 14 ± 6 sprints. Players' mean heart rate (HRmean) and HRmax was 138 ± 23 b·min-1 and 164 ± 20 b·min-1, respectively. There were decrements between halves in TD (p < 0.01, ES = -0.45), RD (p < 0.01, ES = -0.45), maximum speed (p < 0.05, ES = -0.18), HRmax (p < 0.05, ES = -0.23), running (p < 0.01, ES = -0.34), high-speed running (p < 0.01, ES = 0.34), sprinting (p < 0.01, ES = -0.10), HRmax (p < 0.05, ES = -0.23), and HRmax % (p < 0.05, ES = -0.24). Midfielders covered a greater TD compared with full-forwards (p < 0.05, ES = -0.38) and half-forwards (p < 0.05, ES = -0.38). Full-backs covered a significantly lower RD than midfielders (p < 0.05, ES = -1.2), half-backs compared with full-forwards (p < 0.05, ES = 1.14), and half-forwards compared with full-forwards (p < 0.05, ES = 1.15). Full-forwards covered significantly less RD when compared with half-backs (p < 0.05, ES = -1.14), midfielders (p < 0.05, ES = -1.47), and half-forwards (p < 0.05, ES = -1.15). The findings provide physical and physiological values on the match demands of intercounty camogie match-play., (Copyright © 2024 National Strength and Conditioning Association.)

Aim: To develop standardized diagnostic criteria for 'infection-triggered encephalopathy syndrome (ITES)' and five specific clinical syndromes of ITES., Method: The draft definitions were based on existing criteria, standardized, and discussed by a panel of international experts using nominal group technique over 18 months to achieve consensus. All criteria use the same format: (1) presence of infection/fever; (2) clinical features including encephalopathy; (3) neuroradiological features on magnetic resonance imaging; (4) exclusion of other causes., Results: We first highlighted differences between ITES and infectious and autoimmune encephalitis, which is the most important differential diagnosis. Consensus was achieved to define five specific ITESs: acute encephalopathy with biphasic seizures and late reduced diffusion; acute necrotizing encephalopathy; mild encephalopathy with a reversible splenial lesion; acute fulminant cerebral oedema; and acute shock with encephalopathy and multiorgan failure. Two further conditions that are currently classified as epilepsy syndromes but have similar features to ITES, namely febrile infection-related epilepsy syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome, are also discussed., Interpretation: The consensus definition is expected to improve awareness of this disease concept, provide diagnostic framework, and facilitate future international research and clinical trials., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Intraosseous meningiomas are a rare subtype of meningiomas representing approximately 2% of all cases. They can confound a diagnosis of other bone lesions including metastatic tumors. We present a case of a patient with prostate cancer who on staging workup was suspected to have a skull metastasis. Both bone scan and CT Head demonstrated a lesion in the right frontal calvarium. Surgical resection and pathology revealed an intraosseous meningioma. The patient was restaged as having localized prostate cancer and the was offered curative treatment for his malignancy. The case highlights the importance of obtaining tissue diagnosis in cases of radiographic isolated oligometastatic disease in patients with a known primary malignancy., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS)., Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes., Results: We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: ATP1A2, CACNA1A, FOXP1, GRIN1, KCNMA1, KCNQ3, PPFIA3, PUF60, SETD1B, and ZBTB18, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS., Interpretation: DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Post-exposure prophylaxis (PEP) is an efficacious prevention method when initiated promptly after an HIV exposure. Yet, PEP has been underutilized, even among healthcare workers (HCWs) with occupational exposure in sites with PEP policies and procedures and access to PEP medications. It is important to understand the dynamics of uneven PEP use in what appears to be an optimal context to better protect the health and wellbeing of HCWs., Methods: We conducted a scoping review to elucidate factors influencing HCWs' use of PEP after occupational exposure. We searched PubMed, PsychInfo and Google Scholar for peer-reviewed literature published in English from 2014 to 2022 using the terms HIV, postexposure/post-exposure prophylaxis, acceptability, healthcare workers, and values and preferences. An inductive narrative review of the resulting 53 studies identified core themes., Results: Nearly all studies (96%) with various HCW types and settings occurred in low- and middle-income countries (LMICs) in Africa and Asia. Identified themes arrayed along a trajectory of PEP use experience: awareness/knowledge; acceptability; availability/access; uptake/use; adherence/completion. Across studies, awareness of PEP for HIV prevention was high, knowledge about drug regimens and healthcare facility policies was moderate to low; acceptability of PEP was moderate to high; PEP's perceived accessibility/availability was inconsistent and varied by geographic location and setting; HCWs' uptake of PEP was low, affected by not knowing how to report an exposure and being unaware of PEP availability; and adherence/completion of PEP regimens was moderate to low, impeded by side effects and a belief that completing regimens was unnecessary to avert seroconversion. HCWs consistently expressed concern about HIV stigma., Discussion: Findings are limited by the inconsistent use of constructs across studies and a lack of clarity about reporting exposure events. Multi-level approaches are needed to address the interplay of individual, social and structural barriers that diminish HCWs' PEP use. Improved training, incident reporting, 24-hour access to non-stigmatizing PEP services and monitoring of adherence/completion are essential to optimizing HCWs' PEP use., Conclusions: Lessons from HCWs' experience in LMICs may inform understanding of PEP under-use among people in these settings with non-occupational exposures., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Purpose: Early PSA response has been found to be prognostic of outcomes in metastatic hormone sensitive prostate cancer. We performed a secondary analysis of the TITAN trial to determine if early PSA response was predictive of treatment efficacy in metastatic hormone sensitive prostate cancer patients., Materials and Methods: Early PSA response was defined as achieving a PSA level of ≤ 0.2 ng/mL by 6 months of random assignment. A Cox proportional hazard model was constructed in a landmark population with an interaction term between the treatment and early PSA response to determine differential treatment effect on overall survival (OS). We applied multivariable Cox proportional hazard regression model with time to early PSA response fitted with restricted cubic spline to determine the association of time to early PSA response with OS., Results: Approximately 24% (124/524) of patients in the androgen deprivation therapy (ADT) alone group and 61% (321/524) in the apalutamide group had PSA response ≤ 0.2 ng/mL by 6 months. Longer time to early PSA response was associated with significantly superior OS in the apalutamide group. There was a significant difference in treatment effect from apalutamide on OS ( P = .03 for interaction) among 6-month PSA responders (HR: 0.66; 95% CI: 0.44-1.00) vs nonresponders (HR: 1.14; 95% CI: 0.89-1.46). This difference in treatment effect was not statistically significant at 3 months ( P = .17 for interaction). Among 6-month PSA responders, 3-year confounder-adjusted OS was 84% (80%-88%) for the apalutamide group and 74% (66%-82%) for the ADT alone group. Among nonresponders, 3-year adjusted OS for the 2 treatment arms were 58% (52%-65%) and 56% (51%-60%), respectively., Conclusions: Early PSA response by 6 months was a predictor of treatment efficacy from ADT plus apalutamide on OS. Longer time to early PSA response was associated with superior OS in the apalutamide arm.

Purpose: We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer., Methods and Materials: Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions. RT was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity., Results: Overall,123 patients were randomly assigned to either the 3D-CRT (n = 60) or tomotherapy (n = 63) arms. The median follow-up was 161 months. Overall, the proportion of patients with grade ≥ 2 late rectal toxicity was 8.3% (95% CI, 3.1-19.1; n = 5) in the 3D-CRT arm and 11.1% (95% CI, 5.0-22.2; n = 7) in the tomotherapy arm with no significant between-arm difference (P = .83). There was no significant difference (P = .17) in the proportion of patients with late grade ≥ 2 genitourinary toxicity:10.0% (95% CI, 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI, 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the 2 groups (hazard ratio for the tomotherapy arm: 0.72; 95% CI, 0.46-1.15; P = .17)., Conclusions: In this phase 3 trial, the overall incidence of grade ≥ 2 rectal toxicity was low and was not significantly different between the 2 arms. There was no significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Phenotypic plasticity allows a plant cell to alter its structure and function in response to external pressure. This adaptive phenomenon has also been important in the evolution of plants including the emergence of land plants from a streptophyte alga. Penium margaritaceum is a unicellular zygnematophyte (i.e., the group of streptophyte algae that is sister to land plants) that was employed in order to study phenotypic plasticity with a focus on the role of subcellular expansion centers and the cell wall in this process. Live cell fluorescence labeling, immunofluorescence labeling, transmission electron microscopy, and scanning electron microscopy showed significant subcellular changes and alterations to the cell wall. When treated with the actin-perturbing agent, cytochalasin E, cytokinesis is arrested and cells are transformed into pseudo-filaments made of up to eight or more cellular units. When treated with the cyclin-dependent kinase (CDK) inhibitor, roscovitine, cells converted to a unique phenotype with a narrow isthmus zone., (© 2024. The Author(s).)

Background: The American Society for Metabolic and Bariatric Surgery (ASMBS) textbook serves as a comprehensive resource for bariatric surgery, covering recent advancements and clinical questions. Testing artificial intelligence (AI) engines using this authoritative source ensures accurate and up-to-date information and provides insight in its potential implications for surgical education and training., Objectives: To determine the quality and to compare different large language models' (LLMs) ability to respond to textbook questions relating to bariatric surgery., Setting: Remote., Methods: Prompts to be entered into the LLMs were multiple-choice questions found in "The ASMBS Textbook of Bariatric Surgery, second Edition. The prompts were queried into 3 LLMs: OpenAI's ChatGPT-4, Microsoft's Bing, and Google's Bard. The generated responses were assessed based on overall accuracy, the number of correct answers according to subject matter, and the number of correct answers based on question type. Statistical analysis was performed to determine the number of responses per LLMs per category that were correct., Results: Two hundred questions were used to query the AI models. There was an overall significant difference in the accuracy of answers, with an accuracy of 83.0% for ChatGPT-4, followed by Bard (76.0%) and Bing (65.0%). Subgroup analysis revealed a significant difference between the models' performance in question categories, with ChatGPT-4's demonstrating the highest proportion of correct answers in questions related to treatment and surgical procedures (83.1%) and complications (91.7%). There was also a significant difference between the performance in different question types, with ChatGPT-4 showing superior performance in inclusionary questions. Bard and Bing were unable to answer certain questions whereas ChatGPT-4 left no questions unanswered., Conclusions: LLMs, particularly ChatGPT-4, demonstrated promising accuracy when answering clinical questions related to bariatric surgery. Continued AI advancements and research is required to elucidate the potential applications of LLMs in training and education., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Measuring the coverage of HIV prevention services for key populations (KPs) has consistently been a challenge for national HIV programmes. The current frameworks and measurement methods lack emphasis on effective coverage, occur infrequently, lack timeliness and limit the participation of KPs. The Effective Programme Coverage framework, which utilizes a programme science approach, provides an opportunity to assess gaps in various coverage domains and explore the underlying reasons for these gaps, in order to develop targeted solutions. We have demonstrated the application of this framework in partnership with the KP community in Nairobi, Kenya, using an expanded Polling Booth Survey (ePBS) method., Methods: Data were collected between April and May 2023 among female sex workers (FSWs) and men who have sex with men (MSM) using (a) PBS, (b) bio-behavioural survey and (c) focus group discussions. Data collection and analysis involved both KP community and non-community researchers. Descriptive analysis was performed, and proportions were used to assess the programme coverage gaps. The data were weighted to account for the sampling design and unequal selection probabilities. Thematic analysis was conducted on the qualitative data., Results: The condom programme for FSW and MSM had low availability (60.2% and 50.9%), contact (68.8% and 65.9%) and utilization (52.1% and 43.9%) coverages. The pre-exposure prophylaxis (PrEP) programme had very low utilization coverage for FSW and MSM (4.4% and 2.8%), while antiretroviral therapy utilization coverage was higher (86.6% and 87.7%). Reasons for coverage gaps included a low peer educator-to-peer ratio, longer distance to the clinics, shortage of free condoms supplied by the government, experienced and anticipated side effects related to PrEP, and stigma and discrimination experienced in the facilities., Conclusions: The Effective Programme Coverage framework allows programmes to assess coverage gaps and develop solutions and a research agenda targeted at specific domains of coverage with large gaps. The ePBS method works well in collecting data to understand coverage gaps rapidly and allows for the engagement of the KP community., (© 2024 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: The formulation of clinical recommendations pertaining to bariatric surgery is essential in guiding healthcare professionals. However, the extensive and continuously evolving body of literature in bariatric surgery presents considerable challenge for staying abreast of latest developments and efficient information acquisition. Artificial intelligence (AI) has the potential to streamline access to the salient points of clinical recommendations in bariatric surgery., Objectives: The study aims to appraise the quality and readability of AI-chat-generated answers to frequently asked clinical inquiries in the field of bariatric and metabolic surgery., Setting: Remote., Methods: Question prompts inputted into AI large language models (LLMs) and were created based on pre-existing clinical practice guidelines regarding bariatric and metabolic surgery. The prompts were queried into 3 LLMs: OpenAI ChatGPT-4, Microsoft Bing, and Google Bard. The responses from each LLM were entered into a spreadsheet for randomized and blinded duplicate review. Accredited bariatric surgeons in North America independently assessed appropriateness of each recommendation using a 5-point Likert scale. Scores of 4 and 5 were deemed appropriate, while scores of 1-3 indicated lack of appropriateness. A Flesch Reading Ease (FRE) score was calculated to assess the readability of responses generated by each LLMs., Results: There was a significant difference between the 3 LLMs in their 5-point Likert scores, with mean values of 4.46 (SD .82), 3.89 (.80), and 3.11 (.72) for ChatGPT-4, Bard, and Bing (P < .001). There was a significant difference between the 3 LLMs in the proportion of appropriate answers, with ChatGPT-4 at 85.7%, Bard at 74.3%, and Bing at 25.7% (P < .001). The mean FRE scores for ChatGPT-4, Bard, and Bing, were 21.68 (SD 2.78), 42.89 (4.03), and 14.64 (5.09), respectively, with higher scores representing easier readability., Conclusions: LLM-based AI chat models can effectively generate appropriate responses to clinical questions related to bariatric surgery, though the performance of different models can vary greatly. Therefore, caution should be taken when interpreting clinical information provided by LLMs, and clinician oversight is necessary to ensure accuracy. Future investigation is warranted to explore how LLMs might enhance healthcare provision and clinical decision-making in bariatric surgery., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The utility of prostate radiotherapy (RT) is unclear in men with metastatic hormone-sensitive prostate cancer (mHSPC) receiving intensified systemic therapy with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs). We performed a network meta-analysis of randomized controlled trials (RCTs) to investigate the role of prostate RT in low-volume mHSPC., Methods: Bibliographic databases and conference proceedings were searched through July 2023 for RCTs evaluating the addition of ARPIs or prostate RT to standard of care (SOC) systemic therapy, defined as ADT or ADT plus docetaxel, for the initial treatment of mHSPC. We focused exclusively on aggregate data from the low-volume mHSPC subpopulation in these trials. We pooled the treatment arms into four groups: SOC, SOC plus ARPI, SOC plus RT, and SOC plus ARPI plus RT. The primary outcome was overall survival (OS). To compare treatment strategies, a fixed-effects Bayesian network meta-analysis was undertaken, while a Bayesian network meta-regression was performed to account for across-trial differences in docetaxel use as part of SOC and in proportions of patients with de novo presentation., Key Findings and Limitations: Ten RCTs comprising 4423 patients were eligible. The Surface Under the Cumulative Ranking Curve scores were 0.0006, 0.45, 0.62, and 0.94 for SOC, SOC plus RT, SOC plus ARPI, and SOC plus ARPI plus RT, respectively. On a meta-regression, in a population with de novo mHSPC and no docetaxel use, we did not find sufficient evidence of a difference in OS between SOC plus ARPI plus RT versus SOC plus ARPI (hazard ratio [HR]: 0.76; 95% credible interval: 0.51-1.16) and SOC plus RT versus SOC plus ARPI (HR: 1.10; 95% credible interval: 0.92-1.42)., Conclusions and Clinical Implications: There was some evidence that SOC plus ARPI plus RT reduced mortality compared with the next best strategy of SOC plus ARPI in patients with low-volume de novo mHSPC. A meta-analysis with individual patient data or an RCT is needed to confirm these findings., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Haemorrhage control during surgery and following traumatic injury remains a critical, life-saving challenge. Cellulose products are already employed in commercially available haemostatic dressings. This work explores sourcing cellulose from sugarcane trash pulp to produce micro- and nanosized fibres with hydroxyl, carboxylic acid, and trimethylamine functional groups, resulting in either positive or negative surface charges. This paper assesses the influence of these fibres on multiple blood clotting parameters in both dispersed solutions and dry gauze applications. In vitro blood clotting studies demonstrated the significant haemostatic potential of cellulose fibres derived from sugarcane waste to initiate clotting. Plasma absorbance assays showed that the 0.25 mg/mL cellulose microfibre dispersion had the highest clotting performance. It was observed that no single property of surface charge, functionality, or fibre morphology exclusively controlled the clotting initiation measured. Instead, a combination of these factors affected clot formation, with negatively charged cellulose microfibres comprising hydroxyl surface groups providing the most promising result, accelerating the coagulation cascade mechanism by 67% compared to the endogenous activity. This difference in clot initiation shows the potential for the non-wood agricultural waste source of cellulose in haemostatic wound healing applications, contributing to the broader understanding of cellulose-based materials' versatility and their applications in biomedicine.

Communication failures among clinicians in the ICU (intensive care unit) often lead to worse patient outcomes. CritCom is a bilingual (English and Spanish) tool to evaluate the quality of interdisciplinary communication around patient deterioration for pediatric oncology patients. The use of reports, such as the CritCom report, as dissemination methods lead to quicker knowledge translation and implementation of research findings into policy. Nurses and physicians at participating centers who care for patients at risk of deterioration completed the CritCom survey and center-specific reports were generated to communicate CritCom results. Focus groups were conducted with clinicians receiving CritCom reports in both English and Spanish to evaluate report clarity and usability. Participants found the reports to be useful and described the writing and design as clear and specific. Participants provided feedback to improve report design and requested actionable steps to improve communication at their center. Feedback illustrated that the report was easy to interpret and a useful way to disseminate information. Participants noted the utility of the report, illustrating that the use of reports can be a useful method to disseminate research findings back to participants in a way that is applicable to the local context. Communicating research findings through reports can minimize the significant time lag in knowledge translation and provide participants with actionable steps to implement in their setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Counts, Rivera, Wiphatphumiprates, Puerto-Torres, Prewitt, Luke, Graetz, Malone and Agulnik.)

Background: SARS-CoV-2 infection in pregnancy predisposes women and their offspring to adverse health outcomes, while internationally reported rates of vaccination uptake remain low. Our study objective was to quantify the uptake of COVID-19 vaccination in pregnant women, and to assess their attitudes toward vaccination in pregnancy with both quantitative and qualitative analyses., Materials and Methods: This is a prospective, cross-sectional survey at Australia's largest quaternary level maternity centre. A total of 351 pregnant women, at 6-42 weeks gestation receiving antenatal care at our hospital, completed an online voluntary, anonymous, 17 question survey. This was conducted during a five-week period in November to December 2021. The main outcome measures were demographic data, prior SARS-CoV-2 infection and COVID-19 vaccination status, knowledge and attitudes surrounding COVID-19 disease and vaccination in pregnancy., Results: High rates of COVID-19 vaccination were observed in this pregnant population. Of the 351 respondents, 82% had received at least one dose of the COVID 19-vaccination. This increased compared to estimates of 15% in June 2021 which were obtained from the hospital's electronic health record., Conclusions: Our survey demonstrates that a strong public health campaign with clear messaging regarding the beneficial effects of COVID-19 vaccination in pregnancy can lead to high vaccination uptake rates., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

We investigated longitudinal relations between internalizing, externalizing, and total behaviors that challenge in young children on the autism spectrum and mothers' parenting stress. Participants included 93 mothers of children on the autism spectrum aged 27.89-65.84 months, who completed questionnaires on maternal parenting stress, and children's internalizing (anxiety), externalizing (disruptive), and total behaviors that challenge. Data were collected on early intervention program intake and approximately one year later. Cross-sectional findings indicated small to medium effect size associations between internalizing and externalizing behavior and parenting stress. However, cross-lagged structural equation models found that neither internalizing nor externalizing behavior predicted later parenting stress, nor the reverse. Significant stability effects were found for measures of child internalizing (anxiety), externalizing (disruptive), and total behaviors, and parenting stress. Relations between behaviors that challenge and parenting stress over time were non-significant in our models that controlled for stability of behaviors and parenting stress over time. Implications for research and clinical practice, in understanding and targeting the persistence of behaviors that challenge and parenting stress, are discussed., (© 2024. The Author(s).)

Purpose: Pelvic radiation therapy may lead to decreased bone mineral density (BMD) and increased risk of fracture that could be of particular concern in patients with prostate cancer who also receive androgen deprivation therapy (ADT). We performed an exploratory analysis of a randomized, double-masked, placebo-controlled trial to determine whether exposure to prior pelvic external beam radiation therapy (XRT) affects BMD and risk of fracture in patients with prostate cancer treated with ADT., Methods and Materials: Patients with nonmetastatic prostate cancer aged ≥70 years or <70 years with low BMD (T-score < -1) or osteoporotic fracture who had been receiving ADT for ≥12 months were randomly assigned to receive densoumab or placebo every 6 months for 3 years. BMD was measured at baseline and at months 1, 3, 6, 12, 24, and 36. We applied multivariable linear mixed-effects models with an interaction term between the treatment arm and exposure to prior pelvic XRT to evaluate differential XRT effect on percent BMD change between the 2 treatment arms., Results: Among 1407 eligible patients, 31% (n = 447) received prior pelvic XRT. There was no significant difference in any clinical fractures among patients with (5.8%, 26 of 447) or without (5.2%, 50 of 960) prior pelvic XRT (P = .42). Prior pelvic XRT was associated with a significant (0.54%) improvement in BMD (95% CI, 0.05-1.02) in the placebo group and a nonsignificant (0.04%) decline in BMD (95% CI, -0.47 to -0.35) in the denosumab group (interaction P = .007). There was no significant difference in pelvic XRT effect on percent BMD change in the lumbar spine (P = .65) or total hip (P = .39) between the 2 treatment groups., Conclusions: We did not find sufficient evidence to suggest any detrimental effect of pelvic XRT on the treatment effect from denosumab on percent BMD change, with only an approximately 5% incidence of clinical fractures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether part-year or year-round uninsurance is associated with reduced likelihood of using prescription contraception methods rather than using nonprescription methods or using no contraceptive methods. Methods: We identified nonpregnant and sexually active female respondents participating in the National Longitudinal Survey of Youth, 1997 cohort between 2007 and 2019. At each interview, we classified the contraceptive method used most frequently as prescription, nonprescription, or none, and used mixed-effects multinomial logistic regression to predict contraceptive method based on health insurance coverage over the past year (classified as continuous private, continuous public, part-year uninsured, or year-round uninsured). Results: Our sample included 3,738 respondents and 18,678 observations (person-years). In the most recent interview, 35% of respondents used prescription contraception, 16% used nonprescription methods only, and 49% used no method. On multivariable analysis using all available years of data, respondents with part-year uninsurance were 20% less likely to use prescription rather than nonprescription methods, as compared to respondents with continuous private insurance (95% confidence interval: -31%, -6%; p = 0.007), but did not differ on the likelihood of using prescription methods rather than no method. Conclusions: Part-year uninsurance was associated with lower use of prescription contraceptive methods rather than nonprescription methods when compared with continuous private insurance coverage. Use of prescription contraceptives was lowest among people with year-round uninsurance. Policy efforts ensuring continuous insurance coverage with greater flexibility of eligibility and enrollment periods may promote greater access to prescription contraceptives.

Larvae of the southern corn rootworm (SCR) Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae) are primary pests of peanut in the Virginia-Carolina region of the United States, and are relatively sporadic pests in southern states such as Georgia, Alabama, and Florida. Peanuts have strict quality standards which, when they are not met, can diminish crop value by more than 65%. Management of direct pests like SCR is therefore crucial to maintaining the economic viability of the crop. The soil-dwelling nature of SCR larvae complicates management due to difficulties associated with monitoring and predicting infestations. Nonchemical management options are limited in this system; preventative insecticide applications are the most reliable management strategy for at-risk fields. Chlorpyrifos was the standard product for larval SCR management in peanut until its registration was revoked in 2022, leaving no effective chemical management option for larvae. We tested a novel insecticide, isocycloseram, for its ability to reduce pod scarring, pod penetration, and non-SCR pod damage in field studies conducted in Suffolk, Virginia in 2020-2022. Overall injury was low in 2020 and 2022, and in 2022 there was not a significant effect of treatment. In 2021, 2 simulated chemigation applications of isocycloseram in July significantly reduced pod scarring and overall pod injury relative to chlorpyrifos and the untreated control. Our results suggest that isocycloseram may become an effective option for managing SCR in peanut, although more work is needed to understand the mechanisms by which it is effective as a soil-applied insecticide., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3 rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa., Methods: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%., Results: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer., Conclusions: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

Purpose: Trigeminal neuralgia (TN) can be treated on the CyberKnife system using two different treatment delivery paths: the general-purpose full path corrects small rotations, while the dedicated trigeminal path improves dose fall-off but does not allow rotational corrections. The study evaluates the impact of uncorrected rotations on brainstem dose and the length of CN5 (denoted as L eff ) covered by the prescription dose., Methods and Materials: A proposed model estimates the delivered dose considering translational and rotational delivery errors for TN treatments on the CyberKnife system. The model is validated using radiochromic film measurements with and without rotational setup error for both paths. L eff and the brainstem dose is retrospectively assessed for 24 cases planned using the trigeminal path. For 15 cases, plans generated using both paths are compared for the target coverage and toxicity to the brainstem., Results: In experimental validations, measured and estimated doses agree at 1%/1 mm level. For 24 cases, the treated L eff is 5.3 ± 1.7 mm, reduced from 5.9 ± 1.8 mm in the planned dose. Constraints for the brainstem are met in 23 cases for the treated dose but require frequent treatment interruption to maintain rotational corrections <0.5° using the trigeminal path. The treated length of CN5, and plan quality metrics are similar for the two paths, favoring the full path where rotations are corrected., Conclusions: We validated an analytical model that can provide patient-specific tolerances on rotations to meet plan objectives. Treatment using the full path can reduce treatment time and allow for rotational corrections., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment., Competing Interests: Conflict of interest We have no known conflict of interest to disclose.

Purpose: It is unclear whether exposure to commonly prescribed medications influences survival and treatment response in patients with de novo high-risk metastatic prostate cancer (mPCa) treated with androgen receptor pathway inhibitors (ARPIs)., Methods: We performed a secondary analysis of the LATITUDE trial to determine whether receipt of concomitant medications influenced the effect of abiraterone acetate and prednisone, in addition to androgen deprivation therapy (ADT), on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with de novo mPCa. We focused on 7 commonly prescribed classes of medications: metformin, statins, proton pump inhibitors (PPIs), cyclooxygenase 2 (COX-2) inhibitors, aspirin, acetaminophen, and NSAIDs (nonselective COX inhibitors). To account for multiple testing, a two-sided p < 0.0024 was set as the threshold for statistical significance., Results: Overall, 1135 patients were eligible. There was some evidence of a differential treatment effect from abiraterone among patients who received concomitant NSAIDs (hazard ratio [HR] for OS: 0.54; 95% CI: 0.42-0.70) versus those who did not (HR: 0.74; 95% CI: 0.60-0.91), though this did not reach significance (interaction p = 0.05). A similar non-significant finding of heterogeneity of effect from abiraterone was noted among patients who received concomitant aspirin (HR for OS: 0.93 [0.63-1.36]) versus those who did not (HR: 0.61 [0.51-0.73]) (interaction p = 0.04). Receipt of NSAIDs was independently associated with a significantly inferior OS (HR: 1.37 [1.15-1.62]; p < 0.001) and higher relative incidence of PCSM (sHR: 1.47 [1.21-1.78]; p < 0.001)., Conclusions: This exploratory analysis did not find statistically significant evidence of differences in treatment effects from ADT plus abiraterone in de novo high-risk mPCa based on the receipt of concurrent medications. The receipt of NSAIDs was independently associated with increased PCSM and inferior OS., Competing Interests: Declaration of Competing Interest Outside of this work, Dr. Roy reports research grant from Swim Across America. Dr. Spratt reports personal fees from Blue Earth, personal fees from Janssen, personal fees from AstraZeneca, Gammatile, Varian, and Boston Scientific, outside the submitted work. Outside of this work, Dr. Morgan reports personal fees from Astellas, Bayer, Janssen, and TerSera. Dr. Saad reports grants, personal fees, and non-financial support from Janssen, during the conduct of the study; grants, personal fees, and non-financial support from Astellas, grants, personal fees, and non-financial support from Bayer, outside the submitted work. Dr. Wallis has received honoraria from Bayer, EMD Serono, Knight Therapeutics, Haymarket Media, Science & Medicine Canada, TerSera Canada, and Tolmar Pharmaceuticals Canada; reports consulting fees from Janssen Oncology SESEN Bio, and Precision Point Specialty LLC; and has received research funding from Knight Therapeutics outside the submitted work. Dr. Malone has received honoraria from Astellas, Bayer, Janssen, and Sanofi; and travel and accommodations support from TerSera and Sanofi. There are no other conflicts of interest among the other authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

South Africa's PrEP programming has primarily focused on men who have sex with men and other key populations through dedicated clinical and outreach services. However, data shows that the pool of men vulnerable to contracting HIV extends beyond this group, including men who have sex only with women and who do not identify as gay. The aim of this pilot study was to assess acceptability of PrEP among this subset of men who are at risk of HIV acquisition in South Africa and to describe the demographic and behavioral characteristics of male PrEP users as well as their experience of PrEP use. We employed a mixed-methods study design consisting of in-depth interviews and quantitative analysis of routine clinic data collected between September 2021 and February 2022 from 10 private health facilities. Men who enrolled in the study and initiated PrEP had low consistent condom use and nearly three quarters reported more than one sexual partner in the past three months. Despite minimal follow-up support, PrEP persistence was relatively high and similar to other populations. 57% of men returned for their 1-month visit, 40% returned for their 4-month visit, and 16% returned for their 7-month visit. The greatest barriers to ongoing use were the need to take a daily pill and low perceived HIV risk. To improve uptake and continuation, programs should increase awareness of PrEP, leverage trusted sources to build credibility, make access more convenient, and accommodate flexible use through event-driven PrEP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Renal cell carcinoma (RCC) is an uncommon malignancy whose incidence has been increasing over the past few decades, posing treatment challenges for elderly or infirm patients who are not surgical candidates. Stereotactic ablative radiotherapy (SABR) has emerged as a promising non-invasive treatment modality for RCC. The high dose-per-fraction used in SABR overcomes some of the mechanisms of radioresistance that has hindered the effective treatment of RCC with conventional radiotherapy. For primary RCC, local control rates for SABR exceed 90%, with typically minimal grade 3 or higher toxicities, offering a viable alternative for inoperable patients and those not eligible for or unable to tolerate radiofrequency or cryotherapy ablation. SABR can also be used in patients with a solitary kidney as a strategy for renal preservation to avoid need for dialysis. Given its excellent local control rates, low toxicity and preservation of renal function, SABR offers an attractive alternative to more invasive modalities for treatment of localized RCC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dissemination and Implementation science is dedicated to increasing the speed of evidence-based research translated into practice as guided by one or multiple D&I theories, models, and frameworks. The Dissemination and Implementation Models in Health Research and Practice web tool guides users on how to plan, select, combine, adapt, use, and assess theories, models, and frameworks. This paper describes usability testing to update the web tool. Iterative user testing was conducted with implementation science research and clinical participants to facilitate updates and optimize the functionality of the tool. A multi-step protocol involved quantitative and qualitative data collection including a survey, interviews, and a usability testing session. Data from the pre-testing surveys were summarized as frequencies. Data from the usability testing sessions were analyzed using a hybrid adapted deductive rapid matrix qualitative analysis. Data from the interviews were analyzed by deductive a priori coding. Fifteen interviewees represented different research and clinical groups and levels of expertise utilizing D&I TMFs. Participants were purposively selected to represent a range of disciplines and D&I expertise, all invited via one-time email. The 847 total interview comments were reduced by similarity to 259 comments, and 142 were feasible changes fitting the priorities of the web tool. Changes to content, format, and functionality are described in this paper. The iterative usability testing elicited improvements to the web tool including adding more examples, definitions, visuals, and tutorials and simplifying the written content. The web tool remains flexible for additions concerning health equity, de-implementation, and other issues., Supplementary Information: The online version contains supplementary material available at 10.1007/s43477-024-00125-7., Competing Interests: Competing interestThe authors have no conflicts of interest to disclose., (© The Author(s) 2024.)