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In this phase 3 trial, crinecerfont was superior to placebo in reducing elevated androstenedione levels and lowering glucocorticoid doses in pediatric participants with classic congenital adrenal hyperplasia.

Background The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the “Percentage Method”, defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark’s Completeness Index (CCI) also have limitations. Methods We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT) in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT) that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset. Results Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%). Conclusions The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and dropout rates are high.

Background High-quality measurement is critical to advancing knowledge in any field. New fields, such as implementation science, are often beset with measurement gaps and poor quality instruments, a weakness that can be more easily addressed in light of systematic review findings. Although several reviews of quantitative instruments used in implementation science have been published, no studies have focused on instruments that measure implementation outcomes. Proctor and colleagues established a core set of implementation outcomes including: acceptability , adoption , appropriateness , cost , feasibility , fidelity , penetration , sustainability ( Adm Policy Ment Health Ment Health Serv Res 36:24–34, 2009). The Society for Implementation Research Collaboration (SIRC) Instrument Review Project employed an enhanced systematic review methodology ( Implement Sci 2: 2015) to identify quantitative instruments of implementation outcomes relevant to mental or behavioral health settings. Methods Full details of the enhanced systematic review methodology are available ( Implement Sci 2: 2015). To increase the feasibility of the review, and consistent with the scope of SIRC, only instruments that were applicable to mental or behavioral health were included. The review, synthesis, and evaluation included the following: (1) a search protocol for the literature review of constructs; (2) the literature review of instruments using Web of Science and PsycINFO; and (3) data extraction and instrument quality ratings to inform knowledge synthesis. Our evidence-based assessment rating criteria quantified fundamental psychometric properties as well as a crude measure of usability. Two independent raters applied the evidence-based assessment rating criteria to each instrument to generate a quality profile. Results We identified 104 instruments across eight constructs, with nearly half ( n =  50) assessing acceptability and 19 identified for adoption , with all other implementation outcomes revealing fewer than 10 instruments. Only one instrument demonstrated at least minimal evidence for psychometric strength on all six of the evidence-based assessment criteria. The majority of instruments had no information regarding responsiveness or predictive validity. Conclusions Implementation outcomes instrumentation is underdeveloped with respect to both the sheer number of available instruments and the psychometric quality of existing instruments. Until psychometric strength is established, the field will struggle to identify which implementation strategies work best, for which organizations, and under what conditions.

ObjectivesExtension of disease beyond the atrioventricular (AV) node is associated with increased mortality in cardiac neonatal lupus (NL). Treatment of isolated heart block with fluorinated steroids to prevent disease progression has been considered but published data are limited and discordant regarding efficacy. This study evaluated whether fluorinated steroids given to manage isolated advanced block prevented development of disease beyond the AV node and conferred a survival benefit.MethodsIn this retrospective study of cases enrolled in the Research Registry for NL, inclusion was restricted to anti-SSA/Ro-exposed cases presenting with isolated advanced heart block in utero who either received fluorinated steroids within 1 week of detection (N=71) or no treatment (N=85). Outcomes evaluated were: development of endocardial fibroelastosis, dilated cardiomyopathy and/or hydrops fetalis; mortality and pacemaker implantation.ResultsIn Cox proportional hazards regression analyses, fluorinated steroids did not significantly prevent development of disease beyond the AV node (adjusted HR=0.90; 95% CI 0.43 to 1.85; p=0.77), reduce mortality (HR=1.63; 95% CI 0.43 to 6.14; p=0.47) or forestall/prevent pacemaker implantation (HR=0.87; 95% CI 0.57 to 1.33; p=0.53). No risk factors for development of disease beyond the AV node were identified.ConclusionsThese data do not provide evidence to support the use of fluorinated steroids to prevent disease progression or death in cases presenting with isolated heart block.

This article critically reflects upon the social work field engaging the issue of domestic violence and its relationship to the criminal legal system in the USA. The historical trajectory of the contemporary battered women's movement beginning in the 1970s parallels the rise of criminalisation and mass incarceration particularly impacting marginalised racial communities. In the USA, the passage of the Violence against Women Act (VAWA) in 1994 as a part of the Crime Bill symbolises the convergence of historical forces contributing to the growing collaboration between the feminist movement, social work engagement with gender-based violence and the carceral state. Since the late 1990s, new social movement forces including advocates and activists from anti-violence programmes in the USA have contested this unquestioned reliance upon criminal legal remedies and the professionalisation that has depoliticised the social movement. This critique has developed an intersectional analysis that challenges gender-based violence as well as state violence and advanced an alternative set of frameworks and practices. This article employs contributions of critical criminology, critical race theory and empirical examples from the field of domestic violence and new social movements to analyse the limitations of social work policy, practice and research and to suggest future productive directions.

ObjectiveStudies in mouse models implicate complement activation as a causative factor in adverse pregnancy outcomes (APOs). We investigated whether activation of complement early in pregnancy predicts APOs in women with systemic lupus erythematosus (SLE) and/or antiphospholipid (aPL) antibodies.MethodsThe PROMISSE Study enrolled pregnant women with SLE and/or aPL antibodies (n=487) and pregnant healthy controls (n=204) at <12 weeks gestation and evaluated them monthly. APOs were: fetal/neonatal death, preterm delivery <36 weeks because of placental insufficiency or preeclampsia and/or growth restriction <5th percentile. Complement activation products were measured on serial blood samples obtained at each monthly visit.ResultsAPO occurred in 20.5% of SLE and/or aPL pregnancies. As early as 12–15 weeks, levels of Bb and sC5b-9 were significantly higher in patients with APOs and remained elevated through 31 weeks compared with those with normal outcomes. Moreover, Bb and sC5b-9 were significantly higher in patients with SLE and/or aPL without APOs compared with healthy controls. In logistic regression analyses, Bb and sC5b-9 at 12–15 weeks remained significantly associated with APO (ORadj=1.41 per SD increase; 95% CI 1.06 to 1.89; P=0.019 and ORadj=1.37 per SD increase; 95% CI 1.05 to 1.80; P=0.022, respectively) after controlling for demographic and clinical risk factors for APOs in PROMISSE. When analyses were restricted to patients with aPL (n=161), associations between Bb at 12–15 weeks and APOs became stronger (ORadj=2.01 per SD increase; 95% CI 1.16 to 3.49; P=0.013).ConclusionIn pregnant patients with SLE and/or aPL, increased Bb and sC5b-9 detectable early in pregnancy are strongly predictive of APOs and support activation of complement, particularly the alternative pathway, as a contributor to APOs.

Background Lupus patients are at risk for pregnancy loss, and it has been generally accepted that women with SLE should have low disease activity prior to conception. However, there are conflicting results regarding the effect of pregnancy on SLE flares. This study aims to identify predictors of flares during and after pregnancy in SLE patients with inactive or stable disease activity during the first trimester and to characterize and estimate the frequency of post-partum flares in these patients. Methods SLE patients in the multicenter, prospective PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study were evaluated for flares during and after pregnancy using the SELENA-SLEDAI Flare Index. Flares during pregnancy were assessed in all 384 patients and post-partum flares in 234 patients with study visits 2–6 months post-partum. Logistic regression models were fit to the data to identify independent risk factors for flare. Results During pregnancy, 20.8% of patients had mild/moderate flares and 6.25% had severe. Post-partum, 27.7% of patients had mild/moderate flares and 1.7% had severe. The mild flares rarely required treatment. Younger age, low C4 and higher PGA at baseline were independently associated with higher risk of having at least one mild/moderate or severe flare during pregnancy. Older patients were at decreased risk of flare, as well as those with quiescent disease at baseline. No variables evaluated at baseline or the visit most proximal to delivery was significantly associated with risk of flare post-partum. Medications were not associated with flare during or after pregnancy. Conclusion In patients with inactive or stable mild disease activity at the time of conception, lupus disease flares during and after pregnancy are typically mild and occur at similar rates. Flares during pregnancy are predicted by the patients’ age and clinical and serological activity at baseline.

Screening for metabolic dysfunction-associated steatotic liver disease (MASLD) across the entire general population is not currently a recommended strategy. However, it is not uncommon to receive a medical check-up or health check-up for a various of reasons. We tried to investigate whether advanced fibrosis screening in MASLD patients is cost-effective for adults aged 40–49 years during medical or health check-up. The target group for analysis was adults who received medical check-ups for various reasons in the United States. We constructed a hybrid model of the decision tree model and Markov model to compare expected costs and quality-adjusted life-years (QALYs) between ‘screening’ and ‘no screening’ groups from healthcare system perspectives. Patients diagnosed MASLD with advanced fibrosis by FIB4 and VCTE were given intensive lifestyle intervention (ILI). The incremental cost-effectiveness ratio (ICER) was calculated for a 30-year horizon. Assuming effect of ILI is limited to regression of liver fibrosis, ICER of the FIB-4-based two steps algorithm was $103,405 per QALY in adults aged 40–49 years, which was slightly above the threshold value ($100,000/QALY). And in those in adults aged 50–59 and 60–69 years, the ICER was $137,593 and $197,901 per QALY, respectively. If we assume the effect of ILI can improve liver fibrosis as well as cardiovascular disease events, ICERs of screening in aged 40–49 and 50–59 years were $74,596, and $95,974 per QALY, respectively. In an analysis that included additional positive effect on extrahepatic cancer by ILI, estimated ICERs were below the threshold in those in aged 40–49 and 50–59 years. Advanced fibrosis screening in MASLD patients using the FIB-4-based two-step algorithm and ILI was cost-effective for adults aged 40–49 years, taking into account both liver fibrosis and cardiovascular disease.

The objective of our study is to measure perirenal fat thickness using MRI in individuals with steatotic liver disease and investigate the relationship between perirenal fat thickness and metabolic syndrome. This retrospective study included consecutive patients with steatotic liver disease who underwent magnetic resonance imaging-proton density fat fraction from October 2018 to February 2020. Among them, patients with crossed fused kidneys or who underwent nephrectomy were excluded. The metabolic abnormalities were reviewed; presence of hypertension, type 2 diabetes, abdominal circumference, triglyceride, and high-density lipoprotein. Perirenal fat was measured in four directions in both kidneys and the total sum of them was calculated. A total of 250 patients (140 males and 110 females) were included. Perirenal fat thickness showed a moderate correlation with waist circumference, creatinine, and hepatic fat fraction (all p  < 0.001). Perirenal fat thickness was significantly higher in patients with metabolic syndrome than in patients without (76.8 mm vs. 65.1 mm, p  = 0.004). In multivariable regression analysis, the group with high perirenal fat thickness had as significantly higher odd ratio of 2.71 compared to the low group. The perirenal fat thickness is independently associated with metabolic syndrome in patients with steatotic liver disease.

The fluctuating nature of disease activity in systemic lupus erythematosus (SLE), alternating between flares and remissions, poses substantial challenges for its effective management. The use of current biomarkers for monitoring SLE is limited in clinical settings owing to insufficient comprehension of the complex immune involvement underlying the disease course. Here, therefore, we profiled peripheral blood mononuclear cells at both stable and exacerbation states (total of n  = 19) from six patients with SLE and 32 healthy donors using integrated single-cell RNA and T cell receptor (TCR) sequencing. To validate our findings, we analyzed two independent external datasets: bulk RNA sequencing and TCR data from 79 controls and 62 patients with SLE and single-cell RNA sequencing data from 99 healthy controls and 162 patients with SLE. Our analysis revealed cell type-specific activation of interferon-related genes in SLE grouped into four clusters, with elevated activity in disease-associated immune cells. Among these, atypical B cells associated with autoantibody production exhibited distinct differentiation patterns compared with conventional memory B cells, driven by heightened interferon signaling in SLE. Notably, clonal expansion of effector CD8 T cells emerged as a key driver of disease exacerbation, as indicated by reduced TCR diversity. Specific CD8 T cell clonotypes expanded during flare states, transitioning to effector phenotypes that exhibited heightened cytotoxicity and amplified interferon signaling, strongly correlating with tissue damage and flare severity. Our findings establish a critical link between interferon-driven mechanisms and cytotoxic T cell dysfunction in SLE flares, offering potential targets for therapeutic intervention and predictive biomarkers. Atypical B cells and CD8 T cells fuel lupus exacerbations Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects various organs and presents differently in each patient. This study addresses the challenge of understanding the variability of SLE by examining immune cells at a detailed level. The authors used single-cell RNA sequencing to analyze blood samples from six patients with SLE and healthy controls. The study focused on peripheral blood mononuclear cells, which are crucial for the immune response. By examining these cells individually, the researchers identified over 20 distinct cell types involved in SLE. They found that certain immune cells, such as CD8 T cells, were active during disease flare-ups, which are periods of increased symptoms. The results showed that specific gene patterns in these cells could predict disease activity and help classify patients into subtypes. This understanding could lead to more personalized treatments for SLE. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.