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Clinical trials conducted by the Intergroup Rhabdomyosarcoma (RMS) Study Group and the Children's Oncology Group have been pivotal to establishing current standards for diagnosis and therapy for RMS. Recent advancements in understanding the biology and clinical behavior of RMS have led to more nuanced approaches to diagnosis, risk stratification, and treatment. The complexities introduced by these advancements, coupled with the rarity of RMS, pose challenges to conducting large-scale phase 3 clinical trials to evaluate new treatment strategies for RMS. Given these challenges, systematic planning of future clinical trials in RMS is paramount to address pertinent questions regarding the therapeutic efficacy of drugs, biomarkers of response, treatment-related toxicity, and patient quality of life. Herein, the authors outline the proposed strategic approach of the Children's Oncology Group Soft Tissue Sarcoma Committee to the next generation of RMS clinical trials, focusing on five themes: improved novel agent identification and preclinical to clinical translation, more efficient trial development and implementation, expanded opportunities for knowledge generation during trials, therapeutic toxicity reduction and quality of life, and patient engagement., (© 2024 American Cancer Society.)

Introduction: While 10% of pregnant individuals report a penicillin allergy, there is no established best practice for penicillin allergy delabeling in pregnancy. To better understand options for penicillin delabeling, we aimed to evaluate two penicillin allergy delabeling protocols in pregnancy regarding efficacy, adverse events, and patient satisfaction., Material and Methods: From July 2019 to December 2022, we completed a two-center prospective cohort study, where each site recruited pregnant patients over 24 weeks gestational age with a reported penicillin allergy. One center offered antepartum amoxicillin oral challenges, either directly or after negative skin testing (i.e., antepartum oral challenge site). Our other centers completed a two-step approach with antepartum penicillin skin testing only and deferred oral challenges to the postpartum period (i.e., postpartum oral challenge site). Our primary outcome was the rate of penicillin allergy delabeling, defined as tolerating an antibiotic challenge with penicillin or amoxicillin. Univariate analyses were completed using chi-squared, Fisher's exact, and Wilcoxon rank tests., Results: During the study period, 276 pregnant patients were assessed, with 207 in the antepartum oral challenge site and 69 in the postpartum oral challenge site. Among the 204 patients who completed antepartum oral challenges, 201 (98%) passed without reactions. Deferring oral challenges to the postpartum period led to a loss of follow-up for 37/53 (70%) of eligible individuals. Overall, 97% (201/207) of patients at the antepartum oral challenge site were delabeled from their penicillin allergy-compared to 38% (26/69) of patients referred to the postpartum oral challenge site (p < 0.0001). Three antepartum oral challenge reactions were noted, including two mild cutaneous reactions and a case of transient abdominal discomfort., Conclusions: Antepartum amoxicillin oral challenge is a more effective method to delabel pregnant patients from their penicillin allergy. Deferral of oral challenges to the postpartum period introduces a significant barrier for penicillin allergy delabeling., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Incorporating shared decision-making (SDM) with children and families in hospitals was a top priority identified by patients, caregivers, and clinicians. Bronchiolitis, a common and costly reason for hospitalization in children, is an exemplar condition to study SDM in hospitals. Internationally, clinical practice guidelines differ when recommending intravenous (IV or parenteral) or nasogastric (NG or enteral) fluids for hospitalized infants with bronchiolitis who are unsafe to be fed orally. While evidence indicates that either IV or NG fluids are safe and effective, parent involvement in SDM in selecting IV or NG fluids is unknown. Our aim is to generate knowledge of SDM with parents in choosing between IV or NG fluids and the benefits and harms of these two treatment options for hospitalized children with bronchiolitis., Method: This is a multicenter, prospective, observational study, including children aged <12 months admitted to hospital with bronchiolitis requiring supplemental IV or NG fluids. The primary outcome will evaluate the extent of SDM in choosing IV versus NG fluids using the validated CollaboRATE tool. Secondary outcomes include the proportion of parents provided a choice of IV versus NG fluids; parent knowledge of fluid therapy; rate of fluids; length of hospital stay; and complications., Discussion: This study will evaluate the extent of SDM in hospitalized infants with bronchiolitis who require IV or NG fluids and will evaluate both patient-centered and clinical outcomes that are relevant to clinical practice., (© 2024 The Author(s). Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)

Introduction: This exploratory study aimed to assess contact dermatitis (CD) risk among workers using the Manitoba Occupational Disease Surveillance System (MODSS)., Methods: The MODSS linked accepted time-loss claims from the Workers' Compensation Board of Manitoba (2006-2019), with administrative health data from medical and hospital records (1996-2020). CD risk by occupation and industry (hazard ratio, 95% confidence intervals) was estimated using Cox proportional hazard models, adjusted for age and stratified by sex., Results: Increased risk of new onset CD was observed among some occupations and industries with known skin irritants and allergens. Some occupations with known increased risks of CD remained elevated when removing the accepted WCB cases was performed, suggesting that all CD cases in these occupations may not show up in WCB statistics. Increased risk was also observed for occupations and industries with unknown exposures related to CD, whereas some groups known to be at risk of CD were not observed to have elevated risks in this cohort., Discussion: The MODSS successfully identified some occupations and industries known to be at high risk of occupational CD, but not others. Some occupations not typically associated with work-related CD were also identified, which warrants further investigation., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited., Aim: To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code., Methods: REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed., Results: The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients., Conclusions: Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: To characterize non-articular pain (NAP) at early RA diagnosis, the evolution over the first year of treatment, associations with active RA inflammation and impact on remission., Methods: This real-world, longitudinal multi-center cohort study followed participants with active early RA (symptoms<1 year, CDAI>2.8,) enrolled between 1/2017 and 1/2022, and who completed a body pain diagram (BPD) over 1-year. Participants were grouped by prespecified definitions of NAP: 1) none 2) regional or 3) widespread. Rheumatologists performed joint counts. Descriptive statistics summarized the frequency and evolution of NAP patterns over 1-year. Chi-square tests compared the proportions of tender and/or swollen joints by presence of pain in each NAP section. Multi-adjusted GEE regression models estimated associations of NAP patterns with remission outcomes., Results: Participants (N=392) were 70% female, mean(Sd) age of 56(14) years and mean symptoms duration of 5.1(2.7) months. Over half reported NAP at baseline with most (73%) presenting with regional NAP. Common patterns of regional NAP were axial (40%) and pain in upper quadrants (17%). 43% of those with regional NAP persisted or worsened over 1-year, whereas 73% of those with widespread NAP resolved or improved. Joint inflammation was more frequently reported in areas with NAP vs areas without NAP. Regional and widespread NAP were associated with lower odds of reaching CDAI remission (adjusted OR [95%CI]):0.42[0.26 to 0.70] and 0.30[0.12 to 0.74], respectively., Conclusion: Regional NAP is common and persistent in early RA and impacts remission. RA activity may contribute to NAP. More attention to NAP in RA care is warranted., (This article is protected by copyright. All rights reserved.)

Aims: Clinical practice guidelines are commonly written by professional societies in high-income countries (HIC) with limited anticipation of implementation obstacles in other environments. We used heart failure (HF) guidelines as a paradigm to examine this concern, by conducting a survey to understand clinicians' ability to implement HF guidelines and their perceptions of the current HF guideline applicability in low- and middle-income countries (LMIC)., Methods and Results: An online survey of physicians in the database of the Translational Medicine Academy who treat HF patients was offered by email from 5 October to 27 November 2023, inquiring of participants' demographic information, experience, and views of HF guidelines as related to their practice. Of 2622 participating clinicians, 1592 partially completed, and an additional 1030 fully completed the survey. Participants were from 138 countries; 668 practiced in HIC, and 1954 in LMIC. Those from LMIC regarded HF guidelines to be less applicable in their country than did those from HIC (p = 0.0002). Of all those responding, 75.3% indicated that it was somewhat or mostly true that the HF guidelines were mostly applicable to HIC. Those from LMIC, but not HIC indicated that the greatest implementation obstacle was that the guidelines were for HIC (51.3% vs. 43.1%; p = 0.0387). A significantly higher proportion of respondents from LMIC indicated that resources for caring for their patients were somewhat or mostly limiting in most cases, than did those in HIC (41.6% vs. 32.5%, p = 0.0068)., Conclusion: This survey examined the widely-held thought that HF guidelines are broadly applicable to all regions of the world, concluding that such a perception is incorrect. Clinicians from LMIC view the absence of consideration of local resource limitations as the greatest obstacle for guideline implementation. The results regarding HF guidelines likely also have implications for other guidelines and resultant patient outcomes., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Adolescents and young adults (AYAs, 18-39 years) with cancer identifying as racially/ethnically minoritized or 2SLGBTQIA+ (Two-Spirit, lesbian, gay, bisexual, transgender, queer, intersex, asexual and "+" referring to other queer identities) have been underrepresented in cancer research. This study explores the aspects of identity that hold significance for these minoritized AYAs and how these facets impact their healthcare experiences., Methods: Eligible participants comprised English-speaking AYAs who self-identified as racially/ethnically minoritized and/or 2SLGBTQIA+, were diagnosed with cancer between the ages of 15-39, currently aged > 18, and had received or were receiving cancer care within Canadian healthcare system. Additionally, four patient partners meeting the same criteria were recruited as research collaborators. Semi-structured one-on-one virtual interviews guided by an interview script were conducted, and qualitative analysis employed a framework approach., Results: We recruited 23 participants from 4 Canadian provinces (mean age: 28, Range: 20-44); 17 identified as racially/ethnically minoritized, one as sexual/gender minoritized, and five as racially/ethnically and sexually/gender minoritized. Participants emphasized that their culture/ethnicity, religion/spirituality, sexuality, gender, family, career, and being an immigrant are important aspects of their identity, with only one participant recognizing their identity as a "person with cancer". A cancer diagnosis altered the aspects of identity deemed most significant by participants. Both visible and invisible aspects of identity shaped participants' experiences and influenced their level of trust in the healthcare system., Conclusion: Racially, ethnically, gender, or sexually minoritized AYAs with cancer place considerable importance on aspects of their identity that are shaped by their respective communities. Recognizing and respecting these identities are paramount for healthcare professionals to deliver safe and inclusive care., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Background: Novel treatments are needed for patients with advanced, triple-negative breast cancer (TNBC) that progresses or recurs after first-line treatment with chemotherapy. The authors report results from the TNBC cohort of the multicohort, open-label, single-arm, phase 2 LEAP-005 study of lenvatinib plus pembrolizumab in patients with advanced solid tumors (ClinicalTrials.gov identifier NCT03797326)., Methods: Eligible patients had metastatic or unresectable TNBC with disease progression after one or two lines of therapy. Patients received lenvatinib (20 mg daily) plus pembrolizumab (200 mg every 3 weeks; up to 35 cycles). The primary end points were the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1, and safety (adverse events graded by the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0). Duration of response, progression-free survival, and overall survival were secondary end points., Results: Thirty-one patients were enrolled. The objective response rate by investigator assessment was 23% (95% confidence interval [CI], 10%-41%). Overall, the objective response rate by blinded independent central review (BICR) was 32% (95% CI, 17%-51%); and, in patients who had programmed cell death ligand 1 combined positive scores ≥10 (n = 8) and <10 (n = 22), the objective response rate was 50% (95% CI, 16%-84%) and 27% (95% CI, 11%-50%), respectively. The median duration of response by BICR was 12.1 months (range, from 3.0+ to 37.9+ months). The median progression-free survival by BICR was 5.1 months (95% CI, 1.9-11.8 months) and the median overall survival was 11.4 months (95% CI, 4.1-21.7 months). Treatment-related adverse events occurred in 94% of patients (grade 3, 52%; grade 4, 0%). One patient died due to a treatment-related adverse event of subarachnoid hemorrhage., Conclusions: The combination of lenvatinib plus pembrolizumab demonstrated antitumor activity with a manageable safety profile in patients with previously treated, advanced TNBC., (© 2024 Merck Sharp & Dohme LLC and The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: Transitional care of older adults can be highly stressful for informal carers (carers) particularly when they are not involved in preparation and planning with health practitioners. This study aimed to ascertain carer perspectives about the potential acceptability and usability of a tool entitled the TRANSITION tool to support preparation and planning for the transition of an older adult from hospital to home., Design: Exploratory qualitative., Methods: Semi-structured interviews were undertaken between March 2020 and October 2021. A focus group was conducted in July 2022 to seek additional information and support data saturation. A total of 23 participants took part. Data were thematically analysed., Findings: Participants explained their perspectives about the tool in four themes: (1) the TRANSITION tool has value, but health practitioners ask the questions; (2) the TRANSITION tool would be useful and acceptable, but not for all carers; (3) interacting with health practitioners is a barrier to using the tool and to communication; and (4) recognising us as part of the care team., Conclusions: While the tool was found to have potential value and utility, it would only be expected to support carers when they are valued and respected by health practitioners. Leadership is required in healthcare organisations to support genuine care for older adults and their carers, and to enable health practitioners to have time for transitional care communication., Implications for Practice: The findings from the study suggest that the TRANSITION tool could support carers by prompting them about important areas of care to include in communication with health practitioners during discharge preparation., (© 2024 The Author(s). International Journal of Older People Nursing published by John Wiley & Sons Ltd.)

The main objective of this research was to qualitatively examine the impacts of Housing First (HF) specifically on those participants who identified themselves as female in response to question asking what their gender was. The data analyzed are from a larger, muti-site, randomized controlled trial. χ 2 analysis was used to compare the life changes (coded as positive, neutral, or negative) experienced by 64 females (42 HF and 22 TAU). An in-depth qualitative analysis was conducted on 45 of these participants (23 HF and 22 TAU). Significantly more female HF participants reported making positive life changes from baseline to 18-month than those in TAU. Relative to females in TAU, female HF participants reported a number of specific positive changes, including enhanced safety, improved recovery in mental illness, greater reductions in drug use, and individual changes. The implications of findings for strengthening HF programs to meet the unique needs of female participants are discussed., (© 2024 The Author(s). Journal of Community Psychology published by Wiley Periodicals LLC.)

The aquaculture industry is among the fastest growing food production sectors in the world. Land-based aquaculture systems continue to increase in popularity as they offer the benefits of controlling diseases, managing water quality, and minimizing threats to wild populations of fish. However, these systems discharge wastewater high in N and P. The ability of cattail (Typha spp.) constructed wetlands (CWs) to remove N and P from aquaculture wastewater (AWW) was examined here. Cattail CWs were established in mesocosms and had a gradient of AWW applied weekly for a total of 5 weeks. Total N and P loadings ranged from 13.7 to 209.2 mg m -2 and 3.01 to 45.97 mg m -2 over 28 days, respectively. Additions of AWW did not cause elevations in total dissolved N, total ammonia N, or nitrite N in CW water; however, concentrations of nitrate N and P in CW water were related to nutrient loading conditions. Elevations in P persisted for 3-4 weeks among high nutrient loading treatments, providing an opportunity for eutrophic conditions to develop in CW systems. However, after 33 days of treatment, >95% total P concentration reduction was achieved in all mesocosms with final concentrations <0.05 mg L -1 , equivalent to reference conditions. High-loading treatments achieved greater P load reduction (856.8-955.0 mg m -2  year -1 ) than low-loading and reference treatments (591.7-792.7 mg m -2  year -1 ). This study demonstrates the effectiveness of cattail CWs to remove nutrients during AWW treatment and highlights the potential for end-of-season use in northern climates, providing insights regarding the operational timeline of such systems., (© 2024 The Author(s). Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Introduction: The aim of this study was to pilot test a question prompt list (QPL) about cardiovascular disease (CVD) risk reduction after hypertensive pregnancy (HDP)., Methods: In a prospective cohort study of adult women who had HDP given the QPL before and surveyed after a physician visit, we assessed perceived person-centred care, self-efficacy for self-management, perceived self-management and QPL feasibility., Results: Twenty-three women participated: 57% of diverse ethno-cultural groups, 65% < 40 years of age and 48% immigrants. Most scored high for person-centred care (mean 4.1 ± 0.2/5); and moderately for self-efficacy (mean 7.4 ± 0.6/10) and self-management (mean 3.1 ± 0.3/5). Most appreciated QPL design and reported QPL benefits: helped them to prepare for the visit and know what to ask; increased confidence to ask questions, knowledge of the link between HDP and CVD and lifestyle behaviours to reduce CVD risk. Most reported that physicians were receptive to discussing QPL questions., Conclusion: Women appreciated the QPL and knowledge about self-management was high but self-efficacy for or perceived self-management was moderate. It appears feasible to share a QPL with ethno-culturally diverse women who can share it with physicians to facilitate discussions about post-pregnancy HDP-related CVD risk., Patient or Public Contribution: This study involved women who experienced HDP and engaged ethno-culturally diverse women with lived experience of HDP as study advisors in all stages of the research., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

We consider the Bayesian estimation of the parameters of a finite mixture model from independent order statistics arising from imperfect ranked set sampling designs. As a cost-effective method, ranked set sampling enables us to incorporate easily attainable characteristics, as ranking information, into data collection and Bayesian estimation. To handle the special structure of the ranked set samples, we develop a Bayesian estimation approach exploiting the Expectation-Maximization (EM) algorithm in estimating the ranking parameters and Metropolis within Gibbs Sampling to estimate the parameters of the underlying mixture model. Our findings show that the proposed RSS-based Bayesian estimation method outperforms the commonly used Bayesian counterpart using simple random sampling. The developed method is finally applied to estimate the bone disorder status of women aged 50 and older., (© 2024 John Wiley & Sons Ltd.)

Background: The aim of this study was to estimate the event-free survival (EFS) of children and young adults with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) treated in nonrandomized phase 2 studies conducted by the Children's Oncology Group (COG) and predecessor groups to establish a benchmark EFS for future phase 2 NRSTS trials evaluating the activity of novel agents., Methods: A retrospective analysis of patients with recurrent or refractory NRSTS prospectively enrolled in nonrandomized phase 2 COG and predecessor group trials between 1994 and 2015 was conducted. EFS was defined as disease progression/relapse or death and calculated via the Kaplan-Meier method. The log-rank test and relative risk regression were used to compare EFS distribution by age at enrollment, sex, race, NRSTS histology, prior lines of therapy, calendar year of trial, and type of radiographic response., Results: In total, 137 patients were enrolled in 13 phase 2 trials. All trials used radiographic response rate as a primary outcome, and none of the agents used were considered active on the basis of trial-specified thresholds. The estimated median EFS and 6-month EFS of the entire study cohort was 1.5 months (95% confidence interval [CI], 1.3-1.8 months) and 19.4% (95% CI, 12.7%-26%), respectively. No difference in EFS was observed by age at enrollment, sex, race, NRSTS histology subtype, prior lines of therapies, and trial initiation year. EFS significantly differed by radiographic response., Conclusions: The EFS for children and young adults with relapsed or refractory NRSTS remains suboptimal. Established EFS can be referenced as a benchmark for future single-agent phase 2 trials incorporating potentially active novel agents in this population., (© 2024 American Cancer Society.)

Phosphorus (P) and metal accumulation in manured agricultural soils and subsequent losses to waterways have been extensively studied; however, the magnitudes and the factors governing their losses during spring snowmelt flooding are less known. We examined the P and metal release from long-term manured soil to floodwater under simulated snowmelt flooding with recent manure additions. Intact soil columns collected from field plots located in Randolph, Southern Manitoba, 2 weeks after liquid swine manure treatments (surface-applied, injected, or control with no recent manure addition) were flooded and incubated for 8 weeks at 4 ± 1°C to simulate snowmelt conditions. Floodwater (syringe filtered through 0.45 µm) and soil porewater (extracted using Rhizon-Mom samplers) samples were periodically extracted and analyzed for dissolved reactive phosphorus (DRP), pH, zinc (Zn), manganese (Mn), iron (Fe), magnesium (Mg), calcium (Ca), and arsenic (As). Mean floodwater DRP concentrations (mg L -1 ) for manure injected (2.0 ± 0.26), surface-applied (2.6 ± 0.26), and control (2.2 ± 0.26) treatments did not differ significantly. Despite manure application, DRP loss to floodwater did not significantly increase compared to the control, possibly due to the elevated residual soil P at this site from the long-term manure use. At the end of simulated flooding, the DRP concentrations increased by 1.5-fold and 5-fold in porewater and floodwater, respectively. Metal(loid) concentrations were not affected by manure treatments in general, except for Zn and Mg on certain days. Unlike DRP, where porewater and floodwater concentrations increased with time, metalloid concentration in porewater and floodwater did not show consistent trends with flooding time., (© 2024 The Author(s). Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Background: Cardiovascular failure is recognized as a common final pathway at the end of life but there is a paucity of data describing terminal arrhythmias., Aim: We aimed to describe arrhythmias recorded peri-mortem in critically ill patients., Study Design: We enrolled intensive care unit patients admitted to two tertiary Canadian medico-surgical centres. Participants wore a continuous electrocardiogram (ECG) monitor for 14 days, until discharge, removal or death. We recorded all significant occurrences of arrhythmias in the final hour of life., Results: Among 39 patients wearing an ECG monitor at the time of death, 22 (56%) developed at least 1 terminal arrhythmia as adjudicated by an arrhythmia physician: 23% (n = 9) had ventricular fibrillation/polymorphic ventricular tachycardia, 18% (n = 7) had sinoatrial pauses, 15% (n = 6) had atrial fibrillation and 13% (n = 5) had high-degree atrioventricular block. Five participants (13%) developed multiple arrythmias., Conclusions: Arrhythmias are common in dying critically ill patients. There is a roughly even distribution between ventricular arrhythmias, atrial fibrillation, sinus node dysfunction and atrioventricular block., Relevance to Clinical Practice: The results of this study may be most useful for critically ill patients who are organ donation candidates. The appearance of arrhythmias may serve as a marker of change in clinical status for organ donation teams to plan mobilization efforts. In participants who are sedated or intubated, arrhythmias could be a surrogate marker for respiratory or neurologic changes., (© 2024 The Author(s). Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Economists originally developed methods to assess financial catastrophe using total or aggregate out-of-pocket health spending. Aggregate out-of-pocket health spending is financially catastrophic when it exceeds a fixed proportion (i.e., threshold) of a household's total income or expenditure in a given period. However, these methods are now applied to assess financial catastrophe in disease- or service-specific rather than aggregate out-of-pocket health spending without using disease- or service-specific thresholds. This paper argues that not using disease- or service-specific thresholds for such assessments is misleading and underestimates the burden of financial catastrophe, especially among households from poorer backgrounds. It then proposed disease- or service-specific catastrophic payment thresholds, applied them to Nigeria and found that financial catastrophe was underestimated for the five service groups considered. The paper stresses the importance of using disease- or service-specific thresholds and avoiding unadjusted thresholds, which may leave poorer households behind as financially protected., (© 2024 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Aims: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF., Methods and Results: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m 2 , elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials., Conclusions: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Influenza may contribute to coronary/cerebrovascular events and exacerbate underlying conditions., Methods: We used self-controlled case series (SCCS) design to analyze data from US Veterans ≥18 years with coronary/cerebrovascular or exacerbation event +/-1 year of lab-confirmed influenza (LCI) during 2010-2018. We estimated the incidence ratio (IR) (95% CI) of the event for risk interval (Days 1-7 post-LCI) versus control interval (all other times +/-1 year of LCI) with fixed-effects conditional Poisson regression. We included biomarker data for mediation analysis., Results: We identified 3439 episodes with coronary/cerebrovascular-related hospitalizations. IRs (95% CI) for LCI risk versus control interval were STEMI 0.6 (0.1, 4.4), NSTEMI 7.3 (5.8, 9.2), ischemic stroke 4.0 (3.0, 5.4), hemorrhagic stroke 6.2 (3.4, 11.5), and coronary spasm 1.3 (0.5, 3.0). IR significantly increased for NSTEMI and ischemic stroke among those ≥ 65 years. IR for NSTEMI and ischemic stroke dropped 26% and 10%, respectively, when white blood cell (WBC) and platelet count were considered. LCI was significantly associated with exacerbation of preexisting asthma, chronic obstructive pulmonary disease, and congestive heart failure., Conclusions: We found significant association between LCI and hospitalization for NSTEMI, ischemic stroke, and hemorrhagic stroke, the latter possibly due to unaccounted time-varying confounding in SCCS design., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: This study aimed to assess undergraduate dental students' communication skills in relation to patient sociodemographic factors using a three-perspective approach; the student, the patient, and the clinical instructor perspective., Materials and Methods: A cross-sectional study was conducted using validated modified-communication tools; Patient Communication Assessment Instruments (PCAI), Student Communication Assessment Instruments (SCAI), and Clinical Communication Assessment Instruments (CCAI). Moreover, 176 undergraduate clinical year students were recruited in this study whereby each student was assessed by a clinical instructor, a patient, and self-evaluation., Results: The clinical communication skills domains were not significantly influenced by patient sociodemographic factors, including sex, educational background, and the number of visits (p > .05). However, this study revealed a statistically significant difference in the domain of "caring and respectful" of the SCAI between the low- and middle-income groups., Conclusions: Overall, most of the patient sociodemographic factors did not affect clinical communication skills. However, patient income groups played a significant role in one of the communication domains., (© 2024 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Snowmelt runoff is a dominant pathway of phosphorus (P) losses from agricultural lands in cold climatic regions. Soil amendments effectively reduce P losses from soils by converting P to less soluble forms; however, changes in P speciation in cold climatic regions with fall-applied amendments have not been investigated. This study evaluated P composition in soils from a manured field with fall-amended alum (Al 2 (SO 4 ) 3 ·18H 2 O), gypsum (CaSO 4 ·2H 2 O), or Epsom salt (MgSO 4 ·7H 2 O) using three complementary methods: sequential P fractionation, scanning electron microscopy with energy-dispersive X-rays (SEM-EDX) spectroscopy, and P K-edge X-ray absorption near-edge structure spectroscopy (XANES). Plots were established in an annual crop field in southern Manitoba, Canada, with unamended and amended (2.5 Mg ha -1 ) treatments having four replicates in 2020 fall. Soil samples (0-10 cm) taken from each plot soon after spring snowmelt in 2021 were subjected to P fractionation. A composite soil sample for each treatment was analyzed using SEM-EDX and XANES. Alum- and Epsom salt-treated soils had significantly greater residual P fraction with a higher proportion of apatite-like P and a correspondingly lower proportion of P sorbed to calcite (CaCO 3 ) than unamended and gypsum-amended soils. Backscattered electron imaging of SEM-EDX revealed that alum- and Epsom salt-amended treatments had P-enriched microsites frequently associated with aluminum (Al), iron (Fe), magnesium (Mg), and calcium (Ca), which was not observed in other treatments. Induced precipitation of apatite-like species may have been responsible for reduced P loss to snowmelt previously reported with fall application of amendments., (© 2024 The Authors. Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Background and Purpose: Pediatric-onset multiple sclerosis (PoMS) is associated with high health care use. To plan resource allocation for this patient group, knowledge of the incidence rate and prevalence is important. However, such studies are scarce, few are population-based, and the methodology varies widely. We aimed to address this knowledge gap by performing a nationwide study of the incidence rate and prevalence of PoMS in Sweden, an area of high multiple sclerosis (MS) incidence and prevalence., Methods: MS cases were identified by linking two nationwide registers, the National Patient Register and the Swedish MS Registry. MS cases having their first central nervous system demyelinating event or MS clinical onset before age 18 years were classified as pediatric onset. Incidence rate and prevalence were estimated annually over the study period (2006-2016) for the total population and stratified by sex and age group (<12, 12-15, and 16-17 years). Temporal trends and ratios between sexes and age groups were estimated., Results: We identified 238 incident cases from 2006 to 2016, corresponding to an overall crude incidence rate of 1.12 per 100,000 person-years and an overall crude prevalence of 2.82 per 100,000 population. There was a higher incidence rate among females and the highest age category. The overall incidence rate and prevalence estimates remained stable during the study period., Conclusions: Sweden exhibits a consistently high incidence rate and prevalence of PoMS that has remained stable over time. This knowledge serves as a tool to aid in planning resource allocation and health services for this patient population., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Genetic assistant positions are now widely integrated in genetic services to address genetic counselor shortages and ultimately improve efficiency. While over 40% of genetic counselors report working with a genetic assistant ("NSGC Professional Status Survey: Work Environment," 2022), there is limited information about the genetic assistant workforce. The present study surveyed 164 genetic assistants and 139 individuals with experience working with genetic assistants (specifically genetic counselors, residents, geneticists, and administrative staff). Information was collected about genetic assistant demographics, positions, roles and responsibilities, and career paths. The data revealed that the genetic assistant workforce is demographically similar to the genetic counselor workforce and that most genetic assistants intend to pursue a career in genetic counseling. The genetic assistant positions were heterogeneous in terms of the roles and responsibilities assigned, even when separated by work setting. Lastly, participants reported that there were at least 144 genetic assistants across their institutions, a number that has likely grown since the time of the survey. The findings from this study highlight important opportunities for future research and focus, especially development of a scope of practice and competencies for genetic assistants, as well as the potential to use genetic assistant positions as an avenue to improve diversity within the genetic counseling workforce., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Background: Cancer is a leading cause of death among people living with intellectual or developmental disabilities (IDD). Although studies have documented lower cancer screening rates, there is limited epidemiological evidence quantifying potential diagnostic delays. This study explores the risk of metastatic cancer stage for people with IDD compared to those without IDD among breast (female), colorectal, and lung cancer patients in Canada., Methods: Separate population-based cross-sectional studies were conducted in Ontario and Manitoba by linking routinely collected data. Breast (female), colorectal, and lung cancer patients were included (Manitoba: 2004-2017; Ontario: 2007-2019). IDD status was identified using established administrative algorithms. Modified Poisson regression with robust error variance models estimated associations between IDD status and the likelihood of being diagnosed with metastatic cancer. Adjusted relative risks were pooled between provinces using random-effects meta-analyses. Potential effect modification was considered., Results: The final cohorts included 115,456, 89,815, and 101,811 breast (female), colorectal, and lung cancer patients, respectively. Breast (female) and colorectal cancer patients with IDD were 1.60 and 1.44 times more likely to have metastatic cancer (stage IV) at diagnosis compared to those without IDD (relative risk [RR], 1.60; 95% confidence interval [CI], 1.16-2.20; RR, 1.44; 95% CI, 1.24-1.67). This increased risk was not observed in lung cancer. Significant effect modification was not observed., Conclusions: People with IDD were more likely to have stage IV breast and colorectal cancer identified at diagnosis compared to those without IDD. Identifying factors and processes contributing to stage disparities such as lower screening rates and developing strategies to address diagnostic delays is critical., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21-47% and 2-19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0-6%, 3-10%, and 6-20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Massage is widely used for neck pain, but its effectiveness remains unclear., Objectives: To assess the benefits and harms of massage compared to placebo or sham, no treatment or exercise as an adjuvant to the same co-intervention for acute to chronic persisting neck pain in adults with or without radiculopathy, including whiplash-associated disorders and cervicogenic headache., Search Methods: We searched multiple databases (CENTRAL, MEDLINE, EMBASE, CINAHL, Index to Chiropractic Literature, trial registries) to 1 October 2023., Selection Criteria: We included randomised controlled trials (RCTs) comparing any type of massage with sham or placebo, no treatment or wait-list, or massage as an adjuvant treatment, in adults with acute, subacute or chronic neck pain., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane. We transformed outcomes to standardise the direction of the effect (a smaller score is better). We used a partially contextualised approach relative to identified thresholds to report the effect size as slight-small, moderate or large-substantive., Main Results: We included 33 studies (1994 participants analysed). Selection (82%) and detection bias (94%) were common; multiple trials had unclear allocation concealment, utilised a placebo that may not be credible and did not test whether blinding to the placebo was effective. Massage was compared with placebo (n = 10) or no treatment (n = 8), or assessed as an adjuvant to the same co-treatment (n = 15). The trials studied adults aged 18 to 70 years, 70% female, with mean pain severity of 51.8 (standard deviation (SD) 14.1) on a visual analogue scale (0 to 100). Neck pain was subacute-chronic and classified as non-specific neck pain (85%, including n = 1 whiplash), radiculopathy (6%) or cervicogenic headache (9%). Trials were conducted in outpatient settings in Asia (n = 11), America (n = 5), Africa (n = 1), Europe (n = 12) and the Middle East (n = 4). Trials received research funding (15%) from research institutes. We report the main results for the comparison of massage versus placebo. Low-certainty evidence indicates that massage probably results in little to no difference in pain, function-disability and health-related quality of life when compared against a placebo for subacute-chronic neck pain at up to 12 weeks follow-up. It may slightly improve participant-reported treatment success. Subgroup analysis by dose showed a clinically important difference favouring a high dose (≥ 8 sessions over four weeks for ≥ 30 minutes duration). There is very low-certainty evidence for total adverse events. Data on patient satisfaction and serious adverse events were not available. Pain was a mean of 20.55 points with placebo and improved by 3.43 points with massage (95% confidence interval (CI) 8.16 better to 1.29 worse) on a 0 to 100 scale, where a lower score indicates less pain (8 studies, 403 participants; I 2 = 39%). We downgraded the evidence to low-certainty due to indirectness; most trials in the placebo comparison used suboptimal massage doses (only single sessions). Selection, performance and detection bias were evident as multiple trials had unclear allocation concealment, utilised a placebo that may not be credible and did not test whether blinding was effective, respectively. Function-disability was a mean of 30.90 points with placebo and improved by 9.69 points with massage (95% CI 17.57 better to 1.81 better) on the Neck Disability Index 0 to 100, where a lower score indicates better function (2 studies, 68 participants; I 2 = 0%). We downgraded the evidence to low-certainty due to imprecision (the wide CI represents slight to moderate benefit that does not rule in or rule out a clinically important change) and risk of selection, performance and detection biases. Participant-reported treatment success was a mean of 3.1 points with placebo and improved by 0.80 points with massage (95% CI 1.39 better to 0.21 better) on a Global Improvement 1 to 7 scale, where a lower score indicates very much improved (1 study, 54 participants). We downgraded the evidence to low-certainty due to imprecision (single study with a wide CI that does not rule in or rule out a clinically important change) and risk of performance as well as detection bias. Health-related quality of life was a mean of 43.2 points with placebo and improved by 5.30 points with massage (95% CI 8.24 better to 2.36 better) on the SF-12 (physical) 0 to 100 scale, where 0 indicates the lowest level of health (1 study, 54 participants). We downgraded the evidence once for imprecision (a single small study) and risk of performance and detection bias. We are uncertain whether massage results in increased total adverse events, such as treatment soreness, sweating or low blood pressure (RR 0.99, 95% CI 0.08 to 11.55; 2 studies, 175 participants; I 2 = 77%). We downgraded the evidence to very low-certainty due to unexplained inconsistency, risk of performance and detection bias, and imprecision (the CI was extremely wide and the total number of events was very small, i.e < 200 events)., Authors' Conclusions: The contribution of massage to the management of neck pain remains uncertain given the predominance of low-certainty evidence in this field. For subacute and chronic neck pain (closest to 12 weeks follow-up), massage may result in a little or no difference in improving pain, function-disability, health-related quality of life and participant-reported treatment success when compared to a placebo. Inadequate reporting on adverse events precluded analysis. Focused planning for larger, adequately dosed, well-designed trials is needed., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Managing agricultural phosphorus (P) to balance food security and water quality priorities is a massive challenge fraught with uncertainty and competing interests. Throughout his career, Andrew Sharpley addressed this challenge by building our understanding of the fundamental principles and processes that control P behavior in agricultural land, developing tools to assess P losses, and then evaluating and refining nutrient, soil, and water beneficial management practices (BMPs). Together with an exceptionally large and diverse group of collaborators, Sharpley developed, tested, refined, calibrated, and validated management practices and risk assessment tools to develop site-specific recommendations for the right practices, in the right places, and at the right times. This approach has resonated globally, with the strategic use of BMPs in "critical source areas" widely implemented in an effort to improve the effectiveness of BMPs while reducing implementation costs. Additional contributions to nutrient management include determining environmental thresholds for soil test P and measuring the risk of P loss from different sources of P (e.g., various manures and commercial fertilizers). Sharpley's work was also distinctly realistic, ensuring that strategies for mitigating P loss were critically evaluated so that not only were the benefits highlighted, but also that trade-offs were measured. Nowhere is this better illustrated than with trade-offs in particulate P loss and dissolved P loss with conservation tillage. This review summarizes Sharpley's enormous contributions to our knowledge of agricultural P stewardship as well as his model of collaborative, multi-disciplinary leadership, helping the world to maintain agricultural productivity and protect water quality., (© 2024 The Authors. Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)