Primary care clinician perspectives on automated nephrology e-consults for diabetic kidney disease: a pre-implementation qualitative study.

BACKGROUND: Many patients with diabetic kidney disease (DKD) do not receive evidence-based, guideline-recommended treatment shown to reduce DKD progression and complications. Proactive electronic consultations (e-consults) are an emerging intervention strategy that could potentially allow nephrologists to provide timely and evidence-based guidance to primary care providers (PCPs) engaged in early DKD care. METHODS: The objective of this study was to explore perspectives about potential barriers and facilitators associated with a proactive e-consult program to improve DKD care delivery. We conducted semi-structured qualitative interviews with PCPs across three different health systems. Interview transcripts were reviewed in a rapid qualitative analysis approach to iteratively identify, refine, and achieve consensus on a final list of themes and subthemes. RESULTS: A total of 18 interviews were conducted. PCPs across all sites identified similar challenges to delivering guideline-recommended DKD care. PCPs were supportive of the proactive e-consult concept. Three major themes emerged surrounding (1) perceived potential benefits of proactive e-consults, including educational value and improved specialist access; (2) concerns about the proactive nature of e-consults, including the potential to increase PCP workload and the possibility that e-consults could be seen as documenting substandard care; and (3) leveraging of care teams to facilitate recommended DKD care, such as engaging clinic-based pharmacists to implement specialist recommendations from e-consults. CONCLUSION: In this pre-implementation qualitative study, PCPs noted potential benefits and identified concerns and implementation barriers for proactive e-consults for DKD care. Strategies that emerged for promoting successful implementation included involving clinic support staff to enact e-consult recommendations and framing e-consults as a system improvement effort to avoid judgmental associations.

Lessons From the Field From a Volunteer Telehealth Ambassador Program to Enhance Video Visits Among Low-Income Patients: Qualitative Improvement Study.

BACKGROUND: The prevalence of telehealth video use across the United States is uneven, with low uptake in safety-net health care delivery systems, which care for patient populations who face barriers to using digital technologies. OBJECTIVE: This study aimed to increase video visit use in an urban safety-net delivery system. We piloted a telehealth ambassador program, in which volunteers offered technical support to patients with access to digital technologies to convert primary care visits already scheduled as telehealth audio-only visits to telehealth video visits. METHODS: We used a descriptive approach to assess the feasibility, efficacy, and acceptability of the pilot telehealth ambassador program. Feasibility was quantified by the percentage of eligible patients who answered calls from telehealth ambassadors. Program efficacy was measured in two ways: (1) the percentage of patients with access to digital technology who interacted with the navigators and were successfully prepared for a telehealth video visit, and (2) the percentage of prepared patients who completed their scheduled video visits. Program acceptability was ascertained by a structured telephone survey. RESULTS: Telehealth ambassadors attempted to contact 776 eligible patients; 43.6% (338/776) were reached by phone, among whom 44.4% (150/338) were provided digital support between March and May 2021. The mean call duration was 8.8 (range 0-35) minutes. Overall, 67.3% (101/150) of patients who received support successfully completed a telehealth video visit with their provider. Among the 188 patients who were contacted but declined video visit digital support, 61% (114/188) provided a reason for their decline; 42% (48/114) did not see added value beyond a telehealth audio-only visit, 20% (23/114) had insufficient internet access, and 27% (31/114) declined learning about a new technology. The acceptability of the telehealth ambassador program was generally favorable, although some patients preferred having in-real-time technology support on the day of their telehealth video visit. CONCLUSIONS: This high-touch program reached approximately one-half of eligible patients and helped two-thirds of interested patients with basic video visit capability successfully complete a video visit. Increasing the program's reach will require outreach solutions that do not rely solely on phone calls. Routinely highlighting the benefits of video visits, partnering with community-based organizations to overcome structural barriers to telehealth use, and offering in-real-time technology support will help increase the program's efficacy.

Development and validation of a self-updating gout register from electronic health records data.

OBJECTIVE: To develop an automatic gout register from electronic health records (EHRs) data. METHODS: We analysed the EHR of all patients >18 years old from a tertiary academic hospital (2013-2022) based on six criteria: International Classification of Diseases 10 gout diagnosis, urate-lowering therapy prescription, monosodium urate crystals in joint aspiration and gout-related terms in problem lists, clinical or imaging reports. We assessed the positive and negative predictive value (PPV and NPV) of the query by chart reviews. RESULTS: Of 2 110 902 outpatients and inpatients, 10 289 had at least one criterion for gout. The combination of joint aspiration OR diagnostic in the problem list OR≥2 other criteria created a register of 5138 patients, with a PPV of 92.4% (95% CI 88.5% to 95.0%) and an NPV of 94.3% (95% CI 91.9% to 96.0%). PPV and NPV were similar among outpatients and inpatients. Incidence was 2.9 per 1000 person-year and dropped by 30% from the COVID-19 pandemic onward. Patients with gout were on average 71.2 years old (SD 14.9), mainly male (76.5%), overweight (69.5%) and polymorbid (mean number of comorbidities of 3, IQR 1-5). More than half (57.4%) had received a urate-lowering treatment, 6.7% had a gout that led to a hospitalisation or ≥2 flares within a year and 32.9% received a rheumatology consultation. CONCLUSION: An automatic EHR-based gout register is feasible, valid and could be used to evaluate and improve gout management. Interestingly, the register uncovered a marked underdiagnosis or under-reporting of gout since the COVID-19 pandemic.

Comparative effectiveness of baricitinib and alternative biological DMARDs in a Swiss cohort study of patients with RA.

OBJECTIVES: This observational study compares the effectiveness of baricitinib (BARI), a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), with alternative biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA), from a prospective, longitudinal cohort. METHODS: We compared patients initiating a treatment course (TC) of BARI, tumour necrosis factor inhibitors (TNFi) or bDMARDs with other modes of action (OMA), during a period when all these DMARDs were available in Switzerland. The primary outcome was drug maintenance; secondary outcomes included discontinuation rates related specifically to ineffectiveness and adverse events. We further analysed rates of low disease activity (LDA) and remission (REM) at 12 months and drug maintenance in bDMARD-naïve and tsDMARD-naïve population. RESULTS: A total of 1053 TCs were included: 273 on BARI, 473 on TNFi and 307 on OMA. BARI was prescribed to older patients with longer disease duration and more previous treatment failures than TNFi. Compared with BARI, the adjusted drug maintenance was significantly shorter for TNFi (HR for discontinuation: 1.76; 95% CI, 1.32 to 2.35) but not compared with OMA (HR 1.27; 95% CI, 0.93 to 1.72). These results were similar in the b/tsDMARD-naïve population. The higher discontinuation of TNFi was mostly due to increased discontinuation for ineffectiveness (HR 1.49; 95% CI, 1.03 to 2.15), with no significant differences in drug discontinuation for adverse events (HR 1.46; 95% CI, 0.83 to 2.57). The LDA and REM rates at 12 months did not differ significantly between the three groups. CONCLUSIONS: BARI demonstrated a significantly higher drug maintenance compared with TNFi, mainly due to lower drug discontinuations for ineffectiveness. We found no difference in drug maintenance between BARI and OMA. Clinical outcomes did not differ between the three groups. Our results suggest that BARI is an appropriate therapeutic alternative to bDMARDs in the management of RA.

Validation of French versions of the 15-item picker patient experience questionnaire for adults, teenagers, and children inpatients.

Objectives: No French validated concise scales are available for measuring the experience of inpatients in pediatrics. This study aims to adapt the adult PPE-15 to a pediatric population, and translating it in French, as well as to establish reference values for adults, teenagers, and parents of young children. Methods: Cultural adaptation involved forward and backward translations, along with pretests in all three populations. Dimensional structure and internal consistency were assessed using principal component analysis, exploratory factor analysis, and Cronbach's alpha. Construct validity was assessed by examining established associations between patient satisfaction and inpatient variables, including length of stay, and preventable readmission. Results: A total of 25,626 adults, 293 teenagers and 1,640 parents of young children completed the French questionnaires. Factor analysis supported a single dimension (Cronbach's alpha: adults: 0.85, teenagers: 0.82, parents: 0.80). Construct validity showed the expected pattern of association, with dissatisfaction correlating with patient- and stay-related factors, notably length of stay, and readmission. Conclusion: The French versions of the PPE-15 for adults, teenagers and parents of pediatric patients stand as valid and reliable instruments for gauging patient satisfaction regarding their hospital stay after discharge.

Comparison of patients with isolated cutaneous lupus erythematosus versus systemic lupus erythematosus with cutaneous lupus erythematosus as the sole clinical feature: A monocentric study of 149 patients.

BACKGROUND: Cutaneous lupus erythematosus (CLE) may present as an isolated entity or be classified as Systemic lupus erythematosus (SLE) by the presence of laboratory abnormalities, including cytopenia, low complement levels, and/or autoantibodies (CLE with laboratory SLE). OBJECTIVE: To compare isolated CLE and CLE with laboratory SLE and to validate an existing 3-item score with age < 25 years (1 point), phototypes V to VI (1 point), antinuclear antibodies ≥ 1:320 (5 points) to predict the risk of progression from CLE to severe SLE (sSLE). METHODS: Monocentric cohort study including consecutive patients with CLE. CLE with laboratory SLE was defined by 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE score of ≥10 points at baseline with CLE as the sole clinical feature. RESULTS: Of the 149 patients with CLE, 20 had CLE with laboratory SLE. The median follow-up duration was 11.3 years (IQR: 5.1-20.5). Ten patients (7%) had sSLE developed. In survival analysis, the risk of progression to sSLE was higher among CLE with laboratory SLE (hazard ratio = 6.69; 95% CI: 1.93-23.14, P < .001) compared to isolated CLE. In both groups, none of the patients with a risk score ≤ 2 had sSLE developed. LIMITATIONS: Monocentric study with a limited number of patients. CONCLUSIONS: CLE with laboratory patients with SLE have a higher risk of progression to sSLE than isolated CLE.

Development and validation of the physical effort scale (PES).

OBJECTIVES: Previous literature has primarily viewed physical effort as an aversive experience. However, recent research suggests that effort can also be valued positively. These differences in approach and avoidance tendencies toward physical effort may play a key role in the self-regulation of physical activity behaviors. The aim of this study was to develop a scale that measures these tendencies and contributes to a better understanding of physical effort and how it affects behavior. METHODS: The Physical Effort Scale (PES) was developed in Study 1 based on expert evaluations (n = 9) and cognitive interviews (n = 10). In Study 2 (n = 680, 69% female), content validity and dimensional structure were examined using principal component analysis and confirmatory factor analysis. Item reduction was conducted using item response theory. Preliminary construct validity was explored using regression. Study 3 (n = 297, 71% female) was used to validate dimensional structure, internal consistency, and construct validity, and to assess test-retest reliability. RESULTS: In Study 1, 44 items were rated for content validity, of which 18 were selected and refined based on cognitive interviews. Analyses from Study 2 allowed reducing the scale to 8 items with a two-dimension structure: tendency to approach (n = 4) and to avoid physical effort (n = 4). The two subscales showed high internal consistency (α = 0.897 for the approach dimension and 0.913 for the avoidance dimension) and explained usual levels of physical activity, providing preliminary evidence of construct validity. Study 3 confirmed the two-dimension structure with high internal consistency (α = 0.907 and 0.916 for the approach and avoidance dimension, respectively) and revealed acceptable test-retest reliability (intraclass correlation >0.66). Patterns of associations with other constructs showed expected relationships, confirming the concurrent, convergent, and discriminant validity of the scale. CONCLUSIONS: The PES is a valid and reliable measure of individual differences in the valuation of physical effort. This scale can assess the propensity to engage in physically demanding tasks in non-clinical populations. The PES and its manual are available in the Supplementary Material.

Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept: Results from the international TOCERRA and PANABA observational collaborative studies.

OBJECTIVE: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). METHODS: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. RESULTS: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48-0.87] for abatacept, and 1.04 [0.76-1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83-1.47] for abatacept, and 1.30 [0.96-1.78] for tocilizumab. CONCLUSION: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.

A potential role for chlamydial infection in rheumatoid arthritis development.

OBJECTIVES: To assess the relationship between self-reported and serologic evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA-development. METHODS: This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a question on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA-autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA-autoimmunity, RA-associated symptoms and RA-autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against Chlamydia trachomatis' major outer membrane protein. We replicated our analysis in an independent United States-based RA-FDR cohort. RESULTS: Among 1231 RA-FDRs, 168 (13.6%) developed RA-autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA-autoimmunity compared with controls (17.9% vs 9.8%, OR = 2.00, 95%CI: 1.27-3.09, p < 0.01). This association remained significant after adjustments (OR = 1.91, 95%CI: 1.20-2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA-autoimmunity (OR = 3.05, 95% CI: 1.10-8.46, p= 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity. CONCLUSIONS: Self-reported chlamydial infections are associated with elevated RA-autoimmunity in at risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies but is consistent with a role of mucosal origin of RA-related autoimmunity.

The Decrease in Serum Total Cholesterol and Low-Density Lipoprotein (LDL) Concentrations With the Initiation of Hemodialysis Despite a Concomitant Increase in Serum Albumin Concentrations.

Background and objective Hemodialysis patients often have lower serum low-density lipoprotein (LDL) and total cholesterol concentrations compared to the general population. It is unclear if this is due to a persistent decline in the values due to kidney disease or if the hemodialysis itself is contributing to the lower values. It is often assumed that malnutrition and anorexia are the main causes of the low lipid concentration in hemodialysis patients. In this study, we aimed to determine the association between hemodialysis initiation and serum lipid and albumin concentrations. Methodology The medical records of all patients initiating hemodialysis over an 11-year period at a single center were retrospectively reviewed. The data of 145 patients who had all the required lab values available were ultimately included in the study. Serum lipid levels at the initiation of hemodialysis were compared to values obtained mostly 6-18 months later. In order to determine if poor nutritional status is the reason for the decline in serum lipid levels, the serum albumin concentration at the initiation of hemodialysis was compared to that obtained during follow-up labs. Results We observed that serum cholesterol concentration declined from an average of 147 mg/dL to 137 mg/dL, while LDL decreased from an average of 78 mg/dL to 68 mg/dL, and serum albumin concentration increased from 3.4 g/dL to 3.8 g/dL after an average follow-up period of 10.8 months. Conclusions Based on our findings, the decline in serum LDL and total cholesterol concentrations with the initiation of hemodialysis may not be attributed to poor nutritional intake.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

Fulfillment and Validity of the Kidney Health Evaluation Measure for People with Diabetes.

Objective: To evaluate the fulfillment and validity of the kidney health evaluation for people with diabetes (KED) Healthcare Effectiveness Data Information Set (HEDIS) measure. Patients and Methods: Optum Labs Data Warehouse (OLDW) was used to identify the nationally distributed US population aged 18 years and older, with diabetes, between January 1, 2017, and December 31, 2017. The OLDW includes deidentified medical, pharmacy, laboratory, and electronic health record (EHR) data. The KED fulfillment was defined in 2017 as both estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio testing within the measurement year. The KED validity was assessed using bivariate analyses of KED fulfillment with diabetes care measures in 2017 and chronic kidney disease (CKD) diagnosis and evidence-based kidney protective interventions in 2018. Results: Among eligible 5,635,619 Medicare fee-for-service beneficiaries, 736,875 Medicare advantage (MA) beneficiaries, and 660,987 commercial patients, KED fulfillment was 32.2%, 38.7%, and 37.7%, respectively. Albuminuria testing limited KED fulfillment with urinary albumin-creatinine ratio testing (<40%) and eGFR testing (>90%). The KED fulfillment was positively associated with receipt of diabetes care in 2017, CKD diagnosis in 2018, and evidence-based kidney protective interventions in 2018. The KED fulfillment trended lower for Black race, Medicare-Medicaid dual eligibility status, low neighborhood income, and low education status. Conclusion: Less than 40% of adults with diabetes received guideline-recommended testing for CKD in 2017. Routine KED was associated with diabetes care and evidence-based CKD interventions. Increasing guideline-recommended testing for CKD among people with diabetes should lead to timely and equitable CKD detection and treatment.

When Illegitimate Tasks Threaten Patient Safety Culture: A Cross-Sectional Survey in a Tertiary Hospital.

Objectives: The current study investigates the prevalence of illegitimate tasks in a hospital setting and their association with patient safety culture outcomes, which has not been previously investigated. Methods: We conducted a cross-sectional survey in a tertiary referral hospital. Patient safety culture outcomes were measured using the Hospital Survey on Patient Safety Culture questionnaire; the primary outcome measures were a low safety rating for the respondent's unit and whether the respondent had completed one or more safety event reports in the last 12 months. Analyses were adjusted for hospital department and staff member characteristics relating to work and health. Results: A total of 2,276 respondents answered the survey (participation rate: 35.0%). Overall, 26.2% of respondents perceived illegitimate tasks to occur frequently, 8.1% reported a low level of safety in their unit, and 60.3% reported having completed one or more safety event reports. In multivariable analyses, perception of a higher frequency of illegitimate tasks was associated with a higher risk of reporting a low safety rating and with a higher chance of having completed event reports. Conclusion: The prevalence of perceived illegitimate tasks was rather high. A programme aiming to reduce illegitimate tasks could provide support for a causal effect of these tasks on safety culture outcomes.

COVID-19 Vaccination Rate under Different Political Incentive: A Counterfactual Trend Approach Using Nationwide Data.

(1) Background: France implemented a COVID-19 certificate in July 2021 to incentivize the population to uptake COVID-19 vaccines. However, little is known about the variation in its impact across age groups and its dependence on socio-demographic, economic, logistic, or political factors. (2) Methods: Using France's weekly first dose vaccination rate, a counterfactual trend approach allowed for the estimation of the vaccination rate across age groups at a small geographical level before and after the implementation of the health pass. The effect of the health pass was operationalized as the vaccination rate among those who would not be vaccinated without it. (3) Results: Vaccination before the health pass varied greatly among age groups and was mainly influenced by territory (lower in rural and overseas territories when compared to urban and metropolitan ones), political beliefs, and socio-economic disparities. Vaccine logistics played a minor but significant role, while the impact of COVID-19 did not affect the vaccination rate. The health pass increased the vaccination overall but with varying efficiency across groups. It convinced mainly young people politically close to the governmental vaccination strategy and living in urban metropolitan areas with low socio-economical discrepancies. The selected variables explained most of the variability of the vaccination rate before the health pass; they explained, at most, a third of the variation in the health pass effect on vaccination. (4) Conclusions: From a public health perspective, the French health pass increased the overall vaccination, but failed to promote preventive behaviours in all segments of society, particularly in vulnerable communities.

Time to Publication and Time-Lag Publication Bias for Randomized Trials on Connective Tissue Diseases.

OBJECTIVE: To assess the time from completion to publication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs), investigate the factors associated with, and explore the influence of significance of study results on time to publication (time-lag publication bias). METHODS: We included interventional, phase 2/3, 3, or 4 RCTs on CTDs registered in Clinicaltrials.gov from 2000 to 2016, whose results had been published in a peer-review journal less than 5 years after their completion. Main trial features, including the significance of primary outcome results, were collected. Time to publication was the time from study completion to the earliest publication date. Multivariable linear regression was used to identify factors associated with time to publication. RESULTS: We included 62 studies, mostly phase 3 (61%) trials on pharmacologic treatments (94%); we recruited patients with systemic lupus (55%) or systemic sclerosis (23%) and planned to enroll a median of 131 (IQR [interquartile range]: 61-288) patients. Twenty-two (35%) reported at least a statistically significant primary outcome. Median time to publication was 28 months (IQR: 17-36). In a multivariable analysis, time to publication progressively improved over time (faster publication in recent years, with the average time to publication decreasing by 1.3 [95% CI: 0.3-2.3] months per year) and was not influenced by the significance of primary outcome results, funder, impact factor of the journal, number of recruiting countries, and comparator. CONCLUSION: A high proportion of CTDs-RCTs is published beyond 2 years from completion. We did not find evidence of time-lag publication bias, and time to publication improved over time.

EPPO ontology: a semantic-driven approach for plant and pest codes representation.

The agricultural industry and regulatory organizations define strategies and build tools and products for plant protection against pests. To identify different plants and their related pests and avoid inconsistencies between such organizations, an agreed and shared classification is necessary. In this regard, the European and Mediterranean Plant Protection Organization (EPPO) has been working on defining and maintaining a harmonized coding system (EPPO codes). EPPO codes are an easy way of referring to a specific organism by means of short 5 or 6 letter codes instead of long scientific names or ambiguous common names. EPPO codes are freely available in different formats through the EPPO Global Database platform and are implemented as a worldwide standard and used among scientists and experts in both industry and regulatory organizations. One of the large companies that adopted such codes is BASF, which uses them mainly in research and development to build their crop protection and seeds products. However, extracting the information is limited by fixed API calls or files that require additional processing steps. Facing these issues makes it difficult to use the available information flexibly, infer new data connections, or enrich it with external data sources. To overcome such limitations, BASF has developed an internal EPPO ontology to represent the list of codes provided by the EPPO Global Database as well as the regulatory categorization and relationship among them. This paper presents the development process of this ontology along with its enrichment process, which allows the reuse of relevant information available in an external knowledge source such as the NCBI Taxon. In addition, this paper describes the use and adoption of the EPPO ontology within the BASF's Agricultural Solutions division and the lessons learned during this work.

Estimated Prevalence and Testing for Albuminuria in US Adults at Risk for Chronic Kidney Disease.

Importance: Albuminuria testing is crucial for guiding evidence-based treatments to mitigate chronic kidney disease (CKD) progression and cardiovascular morbidity, but it is widely underutilized among persons with or at risk for CKD. Objective: To estimate the extent of albuminuria underdetection from lack of testing and evaluate its association with CKD treatment in a large US cohort of patients with hypertension or diabetes. Design, Setting, and Participants: This cohort study examined adults with hypertension or diabetes, using data from the 2007 to 2018 National Health and Nutrition Examination Surveys (NHANES) and the Optum deidentified electronic health record (EHR) data set of diverse US health care organizations. Analyses were conducted from October 31, 2022, to May 19, 2023. Main Outcomes and Measures: Using NHANES as a nationally representative sample, a logistic regression model was developed to estimate albuminuria (urine albumin-creatinine ratio ≥30 mg/g). This model was then applied to active outpatients in the EHR from January 1, 2017, to December 31, 2018. The prevalence of albuminuria among those with and without albuminuria testing during this period was estimated. A multivariable logistic regression was used to examine associations between having albuminuria testing and CKD therapies within the subsequent year (prescription for angiotensin-converting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB], prescription for sodium-glucose cotransporter 2 inhibitor [SGLT2i], and blood pressure control to less than 130/80 mm Hg or less than 140/90 mm Hg on the latest outpatient measure). Results: The total EHR study population included 192 108 patients (mean [SD] age, 60.3 [15.1] years; 185 589 [96.6%] with hypertension; 50 507 [26.2%] with diabetes; mean [SD] eGFR, 84 [21] mL/min/1.73 m2). There were 33 629 patients (17.5%) who had albuminuria testing; of whom 11 525 (34.3%) had albuminuria. Among 158 479 patients who were untested, the estimated albuminuria prevalence rate was 13.4% (n = 21 231). Thus, only 35.2% (11 525 of 32 756) of the projected population with albuminuria had been tested. Albuminuria testing was associated with higher adjusted odds of receiving ACEi or ARB treatment (OR, 2.39 [95% CI, 2.32-2.46]), SGLT2i treatment (OR, 8.22 [95% CI, 7.56-8.94]), and having blood pressure controlled to less than 140/90 mm Hg (OR, 1.20 [95% CI, 1.16-1.23]). Conclusions and Relevance: In this cohort study of patients with hypertension or diabetes, it was estimated that approximately two-thirds of patients with albuminuria were undetected due to lack of testing. These results suggest that improving detection of CKD with albuminuria testing represents a substantial opportunity to optimize care delivery for reducing CKD progression and cardiovascular complications.

Semaphorin-6D and Plexin-A1 Act in a Non-Cell-Autonomous Manner to Position and Target Retinal Ganglion Cell Axons.

Semaphorins and Plexins form ligand/receptor pairs that are crucial for a wide range of developmental processes from cell proliferation to axon guidance. The ability of semaphorins to act both as signaling receptors and ligands yields a multitude of responses. Here, we describe a novel role for Semaphorin-6D (Sema6D) and Plexin-A1 in the positioning and targeting of retinogeniculate axons. In Plexin-A1 or Sema6D mutant mice of either sex, the optic tract courses through, rather than along, the border of the dorsal lateral geniculate nucleus (dLGN), and some retinal axons ectopically arborize adjacent and lateral to the optic tract rather than defasciculating and entering the target region. We find that Sema6D and Plexin-A1 act together in a dose-dependent manner, as the number of the ectopic retinal projections is altered in proportion to the level of Sema6D or Plexin-A1 expression. Moreover, using retinal in utero electroporation of Sema6D or Plexin-A1 shRNA, we show that Sema6D and Plexin-A1 are both required in retinal ganglion cells for axon positioning and targeting. Strikingly, nonelectroporated retinal ganglion cell axons also mistarget in the tract region, indicating that Sema6D and Plexin-A1 can act non-cell-autonomously, potentially through axon-axon interactions. These data provide novel evidence for a dose-dependent and non-cell-autonomous role for Sema6D and Plexin-A1 in retinal axon organization in the optic tract and dLGN.SIGNIFICANCE STATEMENT Before innervating their central brain targets, retinal ganglion cell axons fasciculate in the optic tract and then branch and arborize in their target areas. Upon deletion of the guidance molecules Plexin-A1 or Semaphorin-6D, the optic tract becomes disorganized near and extends within the dorsal lateral geniculate nucleus. In addition, some retinal axons form ectopic aggregates within the defasciculated tract. Sema6D and Plexin-A1 act together as a receptor-ligand pair in a dose-dependent manner, and non-cell-autonomously, to produce this developmental aberration. Such a phenotype highlights an underappreciated role for axon guidance molecules in tract cohesion and appropriate defasciculation near, and arborization within, targets.