Female Pubertal Development in the United Kingdom: Trends in Onset, Progress and Duration from 1948 to the Present

Female pubertal development is the process of physical changes from the child to adult female bodies. The nature of human adaptation creates huge inter and intra-population variation in female pubertal development in response to both heritable and environmental determinants. Age at menarche has been declining globally in response to urbanisation and industrialisation. In the USA and other developed countries age at pubertal onset, specifically age at thelarche, appears to be declining with the concurrent rise in overweight and obesity. Longitudinal cohort datasets from the UK were analysed to replicate these findings in the UK population from 1948-2005. These data show evidence for a continued downward secular trend in age at menarche, and show a downward secular trend in age at pubertal onset, in response to increased weight status. Over the period 1948-2005, age at menarche decreased by 0.30 years, and age at thelarche decreased by one year. The average interval between pubertal onset and age at menarche increased from 2.3 years to 2.7 years. More than half of the total decrease in age at thelarche took place between 1980 and 2001. Some of the variance in pubertal development, and specifically the large decrease in age at thelarche, may to be the result of increasing exposure to endocrine disrupting chemicals over the last 50-60 years. Lipophilic endocrine disruptors have the potential to accelerate pubertal development in overweight girls who have the capacity to store dangerous levels of these toxic substances in their high fat mass. The changes in timing and tempo of female pubertal development in the UK should be considered on a continuum of adaptive plasticity that is evident in the population variation of female pubertal development, rather than measuring recent changes as pathology. Earlier age at puberty has a number of implications for negative health outcomes, specifically increased risk of reproductive cancers. Moreover, the interaction between increased weight status and increased exposure to endocrine disruptors may exacerbate these negative effects

Understanding Sexual Consent Among Adolescents

Background: Sexual consent remains one of the most important tools in the prevention of sexual violence, for which adolescents are an especially vulnerable group. However, it is unclear how sexual consent processes are defined and used by this population. To bridge this gap in knowledge, we present a protocol for a forthcoming scoping review that will identify and synthesize the available empirical research findings on sexual consent conceptualizations and processes among adolescents. Methods/Design: Using the framework by Arksey and O’Malley (2005), a systematic search of six academic databases (Education Source, ERIC, Gender Studies Database, PsycINFO, Social Services Abstracts, and Sociological Abstracts) will be conducted; this range has been selected due to the multi-disciplinary nature of sexual consent research. Following two levels of screening, data from the full-text articles will be charted and subjected to qualitative thematic analysis. Discussion: These collated results will provide a map of key concepts and establish gaps in the extant literature in order to guide future research on this topic. The findings will advance our knowledge of sexual consent as it is understood by the adolescent population; they may also inform the content and delivery of sexual education programs to ensure that they are relevant to their target audience and assist in the prevention of sexual violence

Investigating the contribution of community empowerment policies to successful co-production: evidence from Scotland

Although frequently perceived as a ‘woolly’ policy concept and a means to reduce public service delivery costs, co-production can lead to increased quality and efficiency of services. In this paper, we explore the contribution of a community empowerment policy to co-production processes. Analysing empirical findings from a mixed-method, longitudinal study through the lens of Myers et al.’s (2017) Theory of Change, the paper develops a model of a successful co-production process. We show that changes in working practices and shifts in power can create friction between co-producing actors. By critiquing specific policies, we inform future co-production research, policy, and practice

Circulating Unmetabolized Folic Acid: Relationship to Folate Status and Effect of Supplementation

There are increasing concerns that exposure to unmetabolized folic acid, which results from folic acid intakes that overwhelm the liver's metabolic capacity, may be associated with adverse effects. In this paper, we examined the folic acid status of women of reproductive age in relation to dietary intake and the effect of folic acid supplementation (1.1 mg or 5 mg). Plasma unmetabolized folic acid was not significantly correlated with folate intake estimated by food frequency questionnaire or biomarkers. The proportion of women with detectable levels of unmetabolized folic acid increased from 65% to 100% after twelve weeks of supplementation (P<0.05); however, the increase in concentrations did not reach statistical significance and the effect was not sustained. Moreover, there were no significant differences between the two doses. This suggests that there are mechanisms by which the body adapts to high folic acid intakes to limit exposure to unmetabolized folic acid

Participation Requests : Evaluation of Part 3 of the Community Empowerment (Scotland) Act 2015

This report presents findings from an evaluation of Part 3 of the Community Empowerment (Scotland) Act 2015 (the Act). Implemented on 1 April 2017, Part 3 of the Act introduced participation requests, offering an opportunity for increased community engagement between community participation bodies and public service authorities. The Scottish Government is statutorily required to evaluate Part 3 of the Act within three years of its enactment and to report on how participation requests are being implemented by public service authorities, utilised by communities, and what impact they have on community empowerment and reduction of inequalities of outcome. The evaluation should also consider the need for an appeals mechanism. As part of the Scottish Government's commitment to review participation requests, a team at Glasgow Caledonian University was commissioned to undertake research to document and evaluate the processes and outcomes related to participation requests, with a particular focus on how Part 3 of the Act addresses (or reproduces) social and economic inequalities

Baseline features of the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial

Aim Describe the distinguishing features of heart failure (HF) patients with reduced ejection fraction (HFrEF) in the VICTORIA (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction) trial. Methods and results Key background characteristics were evaluated in 5050 patients randomized in VICTORIA and categorized into three cohorts reflecting their index worsening HF event. Differences within the VICTORIA population were assessed and compared with PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure). VICTORIA patients had increased risk of mortality and rehospitalization: New York Heart Association class (40% class III), atrial fibrillation (45%), diabetes (47%), hypertension (79%) and mean estimated glomerular filtration rate of 61.5 mL/min/1.73m2. Baseline standard of HF care was very good: 60% received triple therapy. Their N-terminal pro-B-type natriuretic peptide was 3377 pg/mL [interquartile range (IQR) 1992-6380]. Natriuretic peptides were 30% higher level in the 67% patients with HF hospitalization Conclusions VICTORIA comprises a broadly generalizable high-risk population of three unique clinical strata of worsening chronic HFrEF despite very good HF therapy. VICTORIA will establish the role of vericiguat, a soluble guanylate cyclase stimulator, in HFrEF

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial

Background: The prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction included high-risk patients with HF with reduced ejection fraction and a recent worsening HF event. The study participants had a high event rate despite the use of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group. Methods and Results: Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association functional class II–IV) and an ejection fraction of less than 45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical end points, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, and nonlinearities. Optimism-corrected c-indices were calculated using 200 bootstrap samples. Over a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 patients (38.5%). Independent predictors of increased risk for the primary end point included HF characteristics (longer HF duration and worse New York Heart Association functional class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death. Conclusions: Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data—including novel measures—performed well in high-risk patients with HF who were receiving excellent guideline-based clinical care. Clinical Trial Registration: Clinicaltrials.gov identifier, NCT02861534. Lay Summary: Patients with heart failure may benefit from tools that help clinicians to better understand a patient's risk for future events like hospitalization. Relatively few risk models have been created after the worsening of heart failure in a contemporary cohort. We provide insights on the risk factors for clinical events from a recent, large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options

N-Terminal Pro-B-Type Natriuretic Peptide and Clinical Outcomes

OBJECTIVES The purpose of this study was to examine the treatment effect of vericiguat in relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at randomization. BACKGROUND Vericiguat compared with placebo reduced the primary outcome of cardiovascular death (CVD) or heart failure hospitalization (HFH) in patients with HF with reduced ejection fraction (HFrEF) in the VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial. Because an interaction existed between treatment and the primary outcome according to pre-specified quartiles of NT-proBNP at randomization, we examined this further. METHODS This study evaluated the NT-proBNP relationship with the primary outcome in 4,805 of 5,050 patients as a risk-adjusted, tog-transformed continuous variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) are presented. RESULTS Median NT-proBNP was 2,816 pg/ml (25th to 75th percentile: 1,556 to 5,314 pg/ml). The study treatment effect varied across the spectrum of NT-proBNP at randomization (with log(2) transformation, p for interaction = 0.002). A significant association between treatment effects existed in patients with levels 8,000 pg/ml (n = 672), the HR was 1.16 (95% CI: 0.94 to 1.41) for the primary outcome. CONCLUSIONS A reduction in the primary composite endpoint and its CVD and HFH components was observed in patients on vericiguat compared with subjects on placebo with NT-proBNP levels up to 8,000 pg/ml. This provided new insight into the benefit observed in high-risk patients with worsening HFrEF. (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA

Background: Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).Objectives: The authors assessed the association of LVEF with biomarker levels, risk of outcome, and whether the effect of vericiguat was homogeneous across LVEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction) trial.Methods: Patients were grouped by LVEF tertiles (≤24%, 25%-33%, and &gt;33%). Patient characteristics, clinical outcomes, and efficacy and safety of vericiguat were examined by tertile. Prespecified biomarkers including N-terminal pro–B-type natriuretic peptide, cardiac troponin T, growth differentiation factor 15, interleukin 6, high-sensitivity C-reactive protein, and cystatin C were examined.Results: The mean LVEF was 29% ± 8% (range: 5%-45%). A pattern of higher N-terminal pro–B-type natriuretic peptide, high-sensitivity C-reactive protein, and interleukin 6 was evident in patients in the lowest LVEF tertile vs the other tertiles. Patients with lower LVEF experienced higher rates of the composite outcome (41.7%, 36.3%, and 33.4% for LVEF ≤24, 25-33, and &gt;33; P &lt; 0.001). There was no significant treatment effect heterogeneity of vericiguat across LVEF groups (adjusted HR from lowest to highest tertiles: 0.79 [95% CI: 0.68-0.94]; 0.95 [95% CI: 0.82-1.11]; 0.94 [95% CI: 0.79-1.11]; P for interaction = 0.222), although the HR was numerically lower in the lowest tertile. There was also no heterogeneity of effect for CVD and HF hospitalization individually (P interaction for CVD = 0.964; HF hospitalization = 0.438). Discontinuation of treatment because of adverse events, symptomatic hypotension, or syncope was consistent across the range of LVEF.Conclusions: Patients with lower LVEF had a distinctive biomarker profile and a higher risk for adverse clinical outcomes vs those with a higher LVEF. There was no significant interaction for the benefit of vericiguat across LVEF tertiles, although the largest signal for benefit in both the primary outcome and HF hospitalizations was noted in tertile 1 (LVEF ≤24%).</p