"Effects of floating aquatic vegetation and canal sediment on phosphorus in drainage discharges in agricultural canals: A case study in the everglades agricultural area, Florida".

Phosphorus (P) discharge from agricultural and urban drainage is known for causing downstream eutrophication worldwide. Agricultural best management practices that are designed to reduce P load out of farms target different P species from various sources such as fertilizers leaching and farm soil and canal sediment erosion, however, few studies have assessed the impact of floating aquatic vegetation (FAV) on canal sediment and farm drainage water quality. This study evaluated the impact of FAVs on canal sediment properties and P water quality in drainage canals in the Everglades Agricultural Area in south Florida, USA. Non-parametric statistical methods, correlation analysis, trend analysis and principal component analysis (PCA) were used to determine the relationship between FAV coverage with sediment properties and P water quality parameters. Results showed that FAV coverage was correlated with the highly recalcitrant and most stable form of P in the sediment layer (Residual P Pool). FAV coverage also correlated with the dissolved organic P (DOP) which was the smallest P pool (7 %) of total P concentration in drainage water, therefore FAV coverage had no correlation with farm P load. The trend analysis showed no trend in farm P loads, despite a decline in FAV coverage at farm canals over an 8-year period. Phosphorus content in the sediment surface layer was strongly associated with farm P load and had a significant correlation with particulate P (PP) and soluble reactive P (SRP) which constituted 47 % and 46 % of the total P concentration in the drainage water, respectively. Equilibrium P concentration assays also showed the potential to release SRP from the sediment layer. The P budget established for this study reveals that sediment stores the largest P mass (333 kg P), while FAVs store the smallest P mass (8 kg P) in a farm canal, highlighting the significant contribution of canal sediment to farm P discharges. Further research is required to evaluate the impact of sediment removal and canal maintenance practices that help reduce farm P discharges.

APOE ε4 carrier status modifies plasma p-tau181 concentrations in cognitively healthy super-seniors.

INTRODUCTION: This study investigates the effect of apolipoprotein E (APOE) genotype on neurology plasma biomarkers in cognitively healthy Super-Seniors. METHODS: Three hundred seventy plasma specimens from Super-Senior participants ≥ 85 years old, who have never been diagnosed with dementia, cancer, diabetes, cardiovascular, or major pulmonary disease, were analyzed on the Quanterix Simoa HD-X analyzer using commercial Neurology 4-plex E and phosphorylated tau (p-tau)181 assays. RESULTS: Eighty (22%) participants were APOE ε4 carriers and 290 (73%) were non-carriers. No significant differences were found between APOE ε4 carriers and non-carriers regarding age, sex, or Mini-Mental State Examination scores. In APOE ε4 carriers, plasma amyloid beta 42/40 was lower and p-tau181 and glial fibrillary acidic protein were higher compared to non-APOE ε4 carriers. After adjusting for demographic variables, p-tau181 was the only biomarker to remain significantly associated with APOE ε4 carrier status. DISCUSSION: APOE ε4 genotype modifies plasma p-tau181 concentration in seniors resilient to age-related clinical disease, suggesting that some Super-Seniors may have Alzheimer's disease pathology without progressing to cognitive decline. HIGHLIGHTS: Healthy seniors enable identification of associations that may be masked by disease. Plasma phosphorylated tau (p-tau)181 concentrations associate with apolipoprotein E (APOE) ε4 carriership in healthy seniors. APOE should be accounted for when interpreting p-tau181, regardless of disease.

Do we really need cyclophosphamide for lupus nephritis?

A 14-year-old patient presents with hematuria and proteinuria. Clinical evaluation reveals a positive anti-nuclear antibody titer, positive anti-double stranded DNA antibody and hypocomplementemia. Systemic lupus erythematosus (SLE) is diagnosed based on the 2019 EULAR/ACR (European League Against Rheumatism/American College of Rheumatology) classification criteria (Aringer et al. Arthritis Rheumatol 71:1400-1412, 2019). A kidney biopsy is performed that confirms the presence of immune complex glomerulonephritis, ISN-RPS (International Society of Nephrology/Renal Pathology Society) class IV (Bajema et al. Kidney Int 93:789-796, 2018). According to the latest clinical practice guidelines (Rovin et al. Kidney Int 100:753-779, 2021; Fanouriakis et al. Ann Rheum Dis 83:15-29, 2023), there are alternatives to treating this patient with cyclophosphamide. But what if this patient also presented with oliguria and volume overload requiring intensive care and dialysis? What if this patient also presented with altered mental status and seizures, and was diagnosed with neuropsychiatric lupus? What if this patient was also diagnosed with a pulmonary hemorrhage and respiratory failure? The clinical practice guidelines do not address these scenarios that are not uncommon in patients with SLE. Moreover, in some countries worldwide, patients do not have the privilege of access to biologics or more expensive alternatives. The purpose of this review is to evaluate the contemporary options for initial treatment of nephritis in patients with SLE.

Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19.

BACKGROUND: COVID-19 has had a significant impact on people's mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this. METHODS: We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based 'talking therapies' (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare 'do nothing' (baseline) scenarios to 'what if' (mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards. RESULTS: The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50-100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, causes a shift in demand to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand. CONCLUSION: In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.

Perceptions on artificial intelligence-based decision-making for coexisting multiple long-term health conditions: protocol for a qualitative study with patients and healthcare professionals.

INTRODUCTION: Coexisting multiple health conditions is common among older people, a population that is increasing globally. The potential for polypharmacy, adverse events, drug interactions and development of additional health conditions complicates prescribing decisions for these patients. Artificial intelligence (AI)-generated decision-making tools may help guide clinical decisions in the context of multiple health conditions, by determining which of the multiple medication options is best. This study aims to explore the perceptions of healthcare professionals (HCPs) and patients on the use of AI in the management of multiple health conditions. METHODS AND ANALYSIS: A qualitative study will be conducted using semistructured interviews. Adults (≥18 years) with multiple health conditions living in the West Midlands of England and HCPs with experience in caring for patients with multiple health conditions will be eligible and purposively sampled. Patients will be identified from Clinical Practice Research Datalink (CPRD) Aurum; CPRD will contact general practitioners who will in turn, send a letter to patients inviting them to take part. Eligible HCPs will be recruited through British HCP bodies and known contacts. Up to 30 patients and 30 HCPs will be recruited, until data saturation is achieved. Interviews will be in-person or virtual, audio recorded and transcribed verbatim. The topic guide is designed to explore participants' attitudes towards AI-informed clinical decision-making to augment clinician-directed decision-making, the perceived advantages and disadvantages of both methods and attitudes towards risk management. Case vignettes comprising a common decision pathway for patients with multiple health conditions will be presented during each interview to invite participants' opinions on how their experiences compare. Data will be analysed thematically using the Framework Method. ETHICS AND DISSEMINATION: This study has been approved by the National Health Service Research Ethics Committee (Reference: 22/SC/0210). Written informed consent or verbal consent will be obtained prior to each interview. The findings from this study will be disseminated through peer-reviewed publications, conferences and lay summaries.

Pediatric reference intervals for serum neurofilament light and glial fibrillary acidic protein using the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort.

OBJECTIVES: Blood biomarkers have the potential to transform diagnosis and prognosis for multiple neurological indications. Establishing normative data is a critical benchmark in the analytical validation process. Normative data are important in children as little is known about how brain development may impact potential biomarkers. The objective of this study is to generate pediatric reference intervals (RIs) for serum neurofilament light (NfL), an axonal marker, and glial fibrillary acidic protein (GFAP), an astrocytic marker. METHODS: Serum from healthy children and adolescents aged 1 to <19 years were obtained from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. Serum NfL (n=300) and GFAP (n=316) were quantified using Simoa technology, and discrete RI (2.5th and 97.5th percentiles) and continuous RI (5th and 95th percentiles) were generated. RESULTS: While there was no association with sex, there was a statistically significant (p<0.0001) negative association between age and serum NfL (Rho -0.400) and GFAP (Rho -0.749). Two statistically significant age partitions were generated for NfL: age 1 to <10 years (lower, upper limit; 3.13, 20.6 pg/mL) and 10 to <19 years (1.82, 7.44 pg/mL). For GFAP, three statistically significant age partitions were generated: age 1 to <3.5 years (80.4, 601 pg/mL); 3.5 to <11 years (50.7, 224 pg/mL); and 11 to <19 years (26.2, 119 pg/mL). CONCLUSIONS: Taken together with the literature on adults, NfL and GFAP display U-shaped curves with high levels in infants, decreasing levels during childhood, a plateau during adolescence and early adulthood and increasing levels in seniors. These normative data are expected to inform future pediatric studies on the importance of age on neurological blood biomarkers.

Experimentally Induced Pain Results in Reduced Activity of the Rotator Cuff Muscles in Healthy Subjects.

Shoulder pain is a complex, prevalent problem that is multifactorial in nature. While there are many potential causes, one common suspect is the rotator cuff musculature. The purpose of the present study was to induce pain in the supraspinatus muscle of healthy subjects and observe the resulting changes in muscle activity. Eight muscles on 23 subjects were assessed using electromyography: anterior, middle, and posterior deltoid; pectoralis major; upper trapezius; latissimus dorsi; serratus anterior; supraspinatus; and infraspinatus. It was hypothesized that the rotator cuff muscles would display reduced activity during pain, and that reductions in activity would remain after the pain had dissipated. Both of the rotator cuff muscles measured did indeed display reduced activity in a majority of the dynamic, isometric, and maximal contractions. Many of those reductions remained after the pain had subsided.

Laser Epilation as an Adjunct to Standard Care in Reducing Pilonidal Disease Recurrence in Adolescents and Young Adults: A Randomized Clinical Trial.

Importance: Recurrence continues to be a significant challenge in the treatment and management of pilonidal disease. Objective: To compare the effectiveness of laser epilation (LE) as an adjunct to standard care vs standard care alone in preventing recurrence of pilonidal disease in adolescents and young adults. Design, Setting, and Participants: This was a single-institution, randomized clinical trial with 1-year follow-up conducted from September 2017 to September 2022. Patients aged 11 to 21 years with pilonidal disease were recruited from a single tertiary children's hospital. Intervention: LE and standard care (improved hygiene and mechanical or chemical depilation) or standard care alone. Main Outcomes and Measures: The primary outcome was the rate of recurrence of pilonidal disease at 1 year. Secondary outcomes assessed during the 1-year follow-up included disability days, health-related quality of life (HRQOL), health care satisfaction, disease-related attitudes and perceived stigma, and rates of procedures, surgical excisions, and postoperative complications. Results: A total of 302 participants (median [IQR] age, 17 [15-18] years; 157 male [56.1%]) with pilonidal disease were enrolled; 151 participants were randomly assigned to each intervention group. One-year follow-up was available for 96 patients (63.6%) in the LE group and 134 (88.7%) in the standard care group. The proportion of patients who experienced a recurrence within 1 year was significantly lower in the LE treatment arm than in the standard care arm (-23.2%; 95% CI, -33.2 to -13.1; P < .001). Over 1 year, there were no differences between groups in either patient or caregiver disability days, or patient- or caregiver-reported HRQOL, health care satisfaction, or perceived stigma at any time point. The LE group had significantly higher Child Attitude Toward Illness Scores (CATIS) at 6 months (median [IQR], 3.8 [3.4-4.2] vs 3.6 [3.2-4.1]; P = .01). There were no differences between groups in disease-related health care utilization, disease-related procedures, or postoperative complications. Conclusions and Relevance: LE as an adjunct to standard care significantly reduced 1-year recurrence rates of pilonidal disease compared with standard care alone. These results provide further evidence that LE is safe and well tolerated in patients with pilonidal disease. LE should be considered a standard treatment modality for patients with pilonidal disease and should be available as an initial treatment option or adjunct treatment modality for all eligible patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03276065.

Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

Core Components and Implementation Determinants of Multilevel Service Delivery Frameworks Across Child Mental Health Service Settings.

Multilevel service delivery frameworks are approaches to structuring and organizing a spectrum of evidence-based services and supports, focused on assessment, prevention, and intervention designed for the local context. Exemplar frameworks in child mental health include positive behavioral interventions and supports in education, collaborative care in primary care, and systems of care in community mental health settings. Yet, their high-quality implementation has lagged. This work proposes a conceptual foundation for multilevel service delivery frameworks spanning diverse mental health service settings that can inform development of strategic implementation supports. We draw upon the existing literature for three exemplar multilevel service delivery frameworks in different child mental health service settings to (1) identify core components common to each framework, and (2) to highlight prominent implementation determinants that interface with each core component. Six interrelated components of multilevel service delivery frameworks were identified, including, (1) a systems-level approach, (2) data-driven problem solving and decision-making, (3) multiple levels of service intensity using evidence-based practices, (4) cross-linking service sectors, (5) multiple providers working together, including in teams, and (6) built-in implementation strategies that facilitate delivery of the overall model. Implementation determinants that interface with core components were identified at each contextual level. The conceptual foundation provided in this paper has the potential to facilitate cross-sector knowledge sharing, promote generalization across service settings, and provide direction for researchers, system leaders, and implementation intermediaries/practitioners working to strategically support the high-quality implementation of these frameworks.

Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus.

Introduction: Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN. While many studies have linked dysregulation of germinal center formation to SLE pathogenesis, other work supports a role for extrafollicular B cell activation in generation of pathogenic antibody secreting cells. However, whether extrafollicular B cell subsets and their T cell collaborators play a role in specific organ involvement in cLN and/or track with disease activity remains unknown. Methods: We analyzed high-dimensional mass cytometry and gene expression data from 24 treatment naïve cSLE patients at the time of diagnosis and longitudinally, applying novel computational tools to identify abnormalities associated with clinical manifestations (cLN) and disease activity (SLEDAI). Results: cSLE patients have an extrafollicular B cell expansion signature, with increased frequency of i) DN2, ii) Bnd2, iii) plasmablasts, and iv) peripheral T helper cells. Most importantly, we discovered that this extrafollicular signature correlates with disease activity in cLN, supporting extrafollicular T/B interactions as a mechanism underlying pediatric renal pathogenesis. Discussion: This study integrates established and emerging themes of extrafollicular B cell involvement in SLE by providing evidence for extrafollicular B and peripheral T helper cell expansion, along with elevated type 1 IFN activation, in a homogeneous cohort of treatment-naïve cSLE patients, a point at which they should display the most extreme state of their immune dysregulation.

Sociodemographic characteristics and longitudinal progression of multimorbidity: A multistate modelling analysis of a large primary care records dataset in England.

BACKGROUND: Multimorbidity, characterised by the coexistence of multiple chronic conditions in an individual, is a rising public health concern. While much of the existing research has focused on cross-sectional patterns of multimorbidity, there remains a need to better understand the longitudinal accumulation of diseases. This includes examining the associations between important sociodemographic characteristics and the rate of progression of chronic conditions. METHODS AND FINDINGS: We utilised electronic primary care records from 13.48 million participants in England, drawn from the Clinical Practice Research Datalink (CPRD Aurum), spanning from 2005 to 2020 with a median follow-up of 4.71 years (IQR: 1.78, 11.28). The study focused on 5 important chronic conditions: cardiovascular disease (CVD), type 2 diabetes (T2D), chronic kidney disease (CKD), heart failure (HF), and mental health (MH) conditions. Key sociodemographic characteristics considered include ethnicity, social and material deprivation, gender, and age. We employed a flexible spline-based parametric multistate model to investigate the associations between these sociodemographic characteristics and the rate of different disease transitions throughout multimorbidity development. Our findings reveal distinct association patterns across different disease transition types. Deprivation, gender, and age generally demonstrated stronger associations with disease diagnosis compared to ethnic group differences. Notably, the impact of these factors tended to attenuate with an increase in the number of preexisting conditions, especially for deprivation, gender, and age. For example, the hazard ratio (HR) (95% CI; p-value) for the association of deprivation with T2D diagnosis (comparing the most deprived quintile to the least deprived) is 1.76 ([1.74, 1.78]; p < 0.001) for those with no preexisting conditions and decreases to 0.95 ([0.75, 1.21]; p = 0.69) with 4 preexisting conditions. Furthermore, the impact of deprivation, gender, and age was typically more pronounced when transitioning from an MH condition. For instance, the HR (95% CI; p-value) for the association of deprivation with T2D diagnosis when transitioning from MH is 2.03 ([1.95, 2.12], p < 0.001), compared to transitions from CVD 1.50 ([1.43, 1.58], p < 0.001), CKD 1.37 ([1.30, 1.44], p < 0.001), and HF 1.55 ([1.34, 1.79], p < 0.001). A primary limitation of our study is that potential diagnostic inaccuracies in primary care records, such as underdiagnosis, overdiagnosis, or ascertainment bias of chronic conditions, could influence our results. CONCLUSIONS: Our results indicate that early phases of multimorbidity development could warrant increased attention. The potential importance of earlier detection and intervention of chronic conditions is underscored, particularly for MH conditions and higher-risk populations. These insights may have important implications for the management of multimorbidity.

Age specific reference intervals for plasma biomarkers of neurodegeneration and neurotrauma in a Canadian population.

INTRODUCTION: In this study, we aimed to create reference intervals (RI) using a large Canadian population-based cohort, for plasma protein biomarkers with potential utility to screen, diagnosis, prognosticate and manage a variety of neurological diseases and disorders. RIs were generated for: the ratio of amyloid beta 42 over 40 (Aß42/40), phosphorylated tau-181 (p-tau-181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). METHODS: 900 plasma specimens from male and female participants aged 3-79 years old were obtained from the Statistics Canada Biobank, which holds specimens from the Canadian Health Measures Survey. Analysis of Aß42/40, p-tau-181, NfL and GFAP was performed on the Quanterix Simoa HD-X analyzer using the Neurology 4-plex E and p-tau-181 assays. Discrete RIs were produced according to Clinical Laboratory Standards Institute guidelines (EP28-A3c). Continuous RIs were created using quantile regression. RESULTS: For discrete RIs, significant age partitions were determined for each biomarker. No significant sex partitions were found. The following ranges and age partitions were determined: Aß42/40: 3-<55y = 0.053-0.098, 55-<80y = 0.040-0.090; p-tau-181: 3-<12y = 1.4-5.6 pg/ml, 12-<60y = 0.8-3.1 pg/ml, 60-<80y = 0.9-4.0 pg/ml; NfL: 3-<40y = 2.6-11.3 pg/ml, 40-<60y = 4.6-17.7 pg/ml, 60-<80y = 8.1-47.1 pg/ml; GFAP; 3-<10y = 47.0-226 pg/ml, 10-<60y = 21.2-91.9 pg/ml, 60-<80y = 40.7-228 pg/ml. Continuous RIs produced smooth centile curves across the age range, from which point estimates for each year of age were calculated. CONCLUSIONS: Discrete and continuous RIs for neurological plasma biomarkers will help refine normative cut-offs across the lifespan and improve the precision of interpretating biomarker levels. Continuous RIs are recommended for use in age groups, such as pediatrics and older adults, that experience rapid concentration changes by age.

Reducing Unnecessary Oophorectomies for Benign Ovarian Neoplasms in Pediatric Patients.

Importance: Although most ovarian masses in children and adolescents are benign, many are managed with oophorectomy, which may be unnecessary and can have lifelong negative effects on health. Objective: To evaluate the ability of a consensus-based preoperative risk stratification algorithm to discriminate between benign and malignant ovarian pathology and decrease unnecessary oophorectomies. Design, Setting, and Participants: Pre/post interventional study of a risk stratification algorithm in patients aged 6 to 21 years undergoing surgery for an ovarian mass in an inpatient setting in 11 children's hospitals in the United States between August 2018 and January 2021, with 1-year follow-up. Intervention: Implementation of a consensus-based, preoperative risk stratification algorithm with 6 months of preintervention assessment, 6 months of intervention adoption, and 18 months of intervention. The intervention adoption cohort was excluded from statistical comparisons. Main Outcomes and Measures: Unnecessary oophorectomies, defined as oophorectomy for a benign ovarian neoplasm based on final pathology or mass resolution. Results: A total of 519 patients with a median age of 15.1 (IQR, 13.0-16.8) years were included in 3 phases: 96 in the preintervention phase (median age, 15.4 [IQR, 13.4-17.2] years; 11.5% non-Hispanic Black; 68.8% non-Hispanic White); 105 in the adoption phase; and 318 in the intervention phase (median age, 15.0 [IQR, 12.9-16.6)] years; 13.8% non-Hispanic Black; 53.5% non-Hispanic White). Benign disease was present in 93 (96.9%) in the preintervention cohort and 298 (93.7%) in the intervention cohort. The percentage of unnecessary oophorectomies decreased from 16.1% (15/93) preintervention to 8.4% (25/298) during the intervention (absolute reduction, 7.7% [95% CI, 0.4%-15.9%]; P = .03). Algorithm test performance for identifying benign lesions in the intervention cohort resulted in a sensitivity of 91.6% (95% CI, 88.5%-94.8%), a specificity of 90.0% (95% CI, 76.9%-100%), a positive predictive value of 99.3% (95% CI, 98.3%-100%), and a negative predictive value of 41.9% (95% CI, 27.1%-56.6%). The proportion of misclassification in the intervention phase (malignant disease treated with ovary-sparing surgery) was 0.7%. Algorithm adherence during the intervention phase was 95.0%, with fidelity of 81.8%. Conclusions and Relevance: Unnecessary oophorectomies decreased with use of a preoperative risk stratification algorithm to identify lesions with a high likelihood of benign pathology that are appropriate for ovary-sparing surgery. Adoption of this algorithm might prevent unnecessary oophorectomy during adolescence and its lifelong consequences. Further studies are needed to determine barriers to algorithm adherence.

Use of Biostatistical Models to Manage Replicate Error in Concussion Biomarker Research.

Importance: Advancing research on fluid biomarkers associated with sport-related concussion (SRC) highlights the importance of detecting low concentrations using ultrasensitive platforms. However, common statistical practices may overlook replicate errors and specimen exclusion, emphasizing the need to explore robust modeling approaches that consider all available replicate data for comprehensive understanding of sample variation and statistical inferences. Objective: To evaluate the impact of replicate error and different biostatistical modeling approaches on SRC biomarker interpretation. Design, Setting, and Participants: This cross-sectional study within the Surveillance in High Schools to Reduce the Risk of Concussions and Their Consequences study used data from healthy youth athletes (ages 11-18 years) collected from 3 sites across Canada between September 2019 and November 2021. Data were analyzed from November 2022 to February 2023. Exposures: Demographic variables included age, sex, and self-reported history of previous concussion. Main Outcomes and Measures: Outcomes of interest were preinjury plasma glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament-light (NFL), total tau (t-tau) and phosphorylated-tau-181 (p-tau-181) assayed in duplicate. Bland-Altman analysis determined the 95% limits of agreement (LOAs) for each biomarker. The impact of replicate error was explored using 3 biostatistical modeling approaches assessing the associations of age, sex, and previous concussion on biomarker concentrations: multilevel regression using all available replicate data, single-level regression using the means of replicate data, and single-level regression with replicate means, excluding specimens demonstrating more than 20% coefficient variation (CV). Results: The sample included 149 healthy youth athletes (78 [52%] male; mean [SD] age, 15.74 [1.41] years; 51 participants [34%] reporting ≥1 previous concussions). Wide 95% LOAs were observed for GFAP (-17.74 to 18.20 pg/mL), UCH-L1 (-13.80 to 14.77 pg/mL), and t-tau (65.27% to 150.03%). GFAP and UCH-L1 were significantly associated with sex in multilevel regression (GFAP: effect size, 15.65%; ß = -0.17; 95% CI, -0.30 to -0.04]; P = .02; UCH-L1: effect size, 17.24%; ß = -0.19; 95% CI, -0.36 to -0.02]; P = .03) and single-level regression using the means of replicate data (GFAP: effect size, 15.56%; ß = -0.17; 95% CI, -0.30 to -0.03]; P = .02; UCH-L1: effect size, 18.02%; ß = -0.20; 95% CI, -0.37 to -0.03]; P = .02); however, there was no association for UCH-L1 after excluding specimens demonstrating more than 20% CV. Excluding specimens demonstrating more than 20% CV resulted in decreased differences associated with sex in GFAP (effect size, 12.29%; ß = -0.14; 95% CI, -0.273 to -0.004]; P = .04) and increased sex differences in UCH-L1 (effect size, 23.59%; ß = -0.27; 95% CI, -0.55 to 0.01]; P = .06), with the widest 95% CIs (ie, least precision) found in UCH-L1. Conclusions and Relevance: In this cross-sectional study of healthy youth athletes, varying levels of agreement between SRC biomarker technical replicates suggested that means of measurements may not optimize precision for population values. Multilevel regression modeling demonstrated how incorporating all available biomarker data could capture replicate variation, avoiding challenges associated with means and percentage of CV exclusion thresholds to produce more representative estimates of association.

Prevalence and demographic variation of cardiovascular, renal, metabolic, and mental health conditions in 12 million english primary care records.

BACKGROUND: Primary care electronic health records (EHR) are widely used to study long-term conditions in epidemiological and health services research. Therefore, it is important to understand how well the recorded prevalence of these conditions in EHRs, compares to other reliable sources overall, and varies by socio-demographic characteristics. We aimed to describe the prevalence and socio-demographic variation of cardiovascular, renal, and metabolic (CRM) and mental health (MH) conditions in a large, nationally representative, English primary care database and compare with prevalence estimates from other population-based studies. METHODS: This was a cross-sectional study using the Clinical Practice Research Datalink (CPRD) Aurum primary care database. We calculated prevalence of 18 conditions and used logistic regression to assess how this varied by age, sex, ethnicity, and socio-economic status. We searched the literature for population prevalence estimates from other sources for comparison with the prevalences in CPRD Aurum. RESULTS: Depression (16.0%, 95%CI 16.0-16.0%) and hypertension (15.3%, 95%CI 15.2-15.3%) were the most prevalent conditions among 12.4 million patients. Prevalence of most conditions increased with socio-economic deprivation and age. CRM conditions, schizophrenia and substance misuse were higher in men, whilst anxiety, depression, bipolar and eating disorders were more common in women. Cardiovascular risk factors (hypertension and diabetes) were more prevalent in black and Asian patients compared with white, but the trends in prevalence of cardiovascular diseases by ethnicity were more variable. The recorded prevalences of mental health conditions were typically twice as high in white patients compared with other ethnic groups. However, PTSD and schizophrenia were more prevalent in black patients. The prevalence of most conditions was similar or higher in the primary care database than diagnosed disease prevalence reported in national health surveys. However, screening studies typically reported higher prevalence estimates than primary care data, especially for PTSD, bipolar disorder and eating disorders. CONCLUSIONS: The prevalence of many clinically diagnosed conditions in primary care records closely matched that of other sources. However, we found important variations by sex and ethnicity, which may reflect true variation in prevalence or systematic differences in clinical presentation and practice. Primary care data may underrepresent the prevalence of undiagnosed conditions, particularly in mental health.

Cognitive dysfunction in pediatric systemic lupus erythematosus: current knowledge and future directions.

Cognitive dysfunction (CD) is a neurologic complication of pediatric systemic lupus erythematosus (SLE) that remains poorly understood and understudied, despite the potential negative effects of CD on long-term socioeconomic status and quality of life. Data regarding the prevalence and risk factors for CD in pediatric SLE as well as the optimal screening, treatment, and long-term outcomes for CD are lacking. In this review, we present current knowledge on CD in pediatric SLE with a focus on the application to clinical practice. We discuss the challenges in diagnosis, clinical screening methods, potential impacts, and interventions for this complication. Finally, we discuss the remaining gaps in our knowledge of CD in pediatric SLE, and avenues for future research efforts.

Inequities in the Diagnosis of Pediatric Appendicitis in Tertiary Children's Hospitals and the Consequences of Delayed Diagnosis.

INTRODUCTION: Missed diagnosis (MD) of acute appendicitis is associated with increased risk of appendiceal perforation. This study aimed to investigate whether racial/ethnic disparities exist in the diagnosis of pediatric appendicitis by comparing rates of MD versus single-encounter diagnosis (SED) between racial/ethnic groups. METHODS: Patients 0-18 y-old admitted for acute appendicitis from February 2017 to December 2021 were identified in the Pediatric Health Information System (PHIS). International Classification of Diseases, 10th Revision, Clinical Modification diagnosis codes for Emergency Department visits within 7 d prior to diagnosis were evaluated to determine whether the encounter represented MD. Generalized mixed models were used to assess the association between MD and patient characteristics. A similar model assessed independent predictors of perforation. RESULTS: 51,164 patients admitted for acute appendicitis were included; 50,239 (98.2%) had SED and 925 (1.8%) had MD. Compared to non-Hispanic White patients, patients of non-Hispanic Black (odds ratio 2.5, 95% confidence interval 2.0-3.1), Hispanic (2.1, 1.8-2.5), and other race/ethnicity (1.6, 1.2-2.1) had higher odds of MD. There was a significant interaction between race/ethnicity and imaging (P < 0.0001). Among patients with imaging, race/ethnicity was not significantly associated with MD. Among patients without imaging, there was an increase in strength of association between race/ethnicity and MD (non-Hispanic Black 3.6, 2.7-4.9; Hispanic 3.3, 2.6-4.1; other 2.0, 1.4-2.8). MD was associated with increased risk of perforation (2.5, 2.2-2.8). CONCLUSIONS: Minority children were more likely to have MD. Future efforts should aim to mitigate the risk of MD, including implementation of algorithms to standardize the workup of abdominal pain to reduce potential consequences of implicit bias.

Nitrogen and phosphorous acquisition strategies drive coexistence patterns among archaeal lineages in soil.

Soil represents the largest reservoir of Archaea on Earth. Present-day archaeal diversity in soils globally is dominated by members of the class Nitrososphaeria. The evolutionary radiation of this class is thought to reflect adaptations to a wide range of temperatures, pH, and other environmental conditions. However, the mechanisms that govern competition and coexistence among Nitrososphaeria lineages in soil remain poorly understood. Here we show that predominant soil Nitrososphaeria lineages compose a patchwork of gene inventory and expression profiles for ammonia, urea, and phosphate utilization. In contrast, carbon fixation, respiration, and ATP synthesis genes are conserved and expressed consistently among predominant phylotypes across 12 major evolutionary lineages commonly found in soil. In situ gene expression profiles closely resemble pure culture reference strains under optimal growth conditions. Together, these results reveal resource-based coexistence patterns among Nitrososphaeria lineages and suggest complementary ecophysiological niches associated with differential nutrient acquisition strategies among globally predominant archaeal lineages in soil.