bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive clinical trial designs with blinded selection of binary composite endpoints and sample size reassessment
Authors: Roig Marta Bofill , Melis Guadalupe Gómez , Posch Martin , Koenig Franz 
Published: September 2022

Summary
For randomized clinical trials where a single, primary, binary endpoint would require unfeasibly large sample sizes, composite endpoints (CEs) are widely chosen as the primary endpoint. Despite being commonly used, CEs entail challenges in designing and interpreting results. Given that the components may be of different relevance and have different effect sizes, the choice of components must be made carefully. Especially, sample size calculations for composite binary endpoints depend not only on the anticipated effect sizes and event probabilities of the composite components but also on the correlation between them. However, information on the correlation between endpoints is usually not reported in the literature which can be an obstacle for designing future sound trials. We consider two-arm randomized controlled trials with a primary composite binary endpoint and an endpoint that consists only of the clinically more important component of the CE. We propose a trial design that allows an adaptive modification of the primary endpoint based on blinded information obtained at an interim analysis. Especially, we consider a decision rule to select between a CE and its most relevant component as primary endpoint. The decision rule chooses the endpoint with the lower estimated required sample size. Additionally, the sample size is reassessed using the estimated event probabilities and correlation, and the expected effect sizes of the composite components. We investigate the statistical power and significance level under the proposed design through simulations. We show that the adaptive design is equally or more powerful than designs without adaptive modification on the primary endpoint. Besides, the targeted power is achieved even if the correlation is misspecified at the planning stage while maintaining the type 1 error. All the computations are implemented in R and illustrated by means of a peritoneal dialysis trial.
Lower affective empathy in oral contraceptive users: a cross-sectional fMRI study
Authors: Kimmig Ann-Christin Sophie , Wildgruber Dirk , Gärtner Anna , Drotleff Bernhard , Krylova Marina , Lämmerhofer Michael , Sundström-Poromaa Inger , Derntl Birgit 
Published: September 2022

AbstractEvidence accumulates that oral contraceptive (OC) use modulates various socio-affective behaviors, including empathic abilities. Endogenous and synthetic sex hormones, such as estrogens and progestogens, bind to receptor sites in brain regions (i.e. frontal, limbic, and cerebellar) involved in socio-affective processing. Therefore, the aim of this study was to investigate the role of OC use in empathy. In a cross-sectional functional magnetic resonance imaging study, women in different hormonal states, including OC use (n = 46) or being naturally cycling in the early follicular (fNC: n = 37) or peri-ovulatory phase (oNC: n = 28), performed a visual, sentence-based empathy task. Behaviorally, OC users had lower empathy ratings than oNC women. Congruently, whole-brain analysis revealed significantly larger task-related activation of several brain regions, including the left dorsomedial prefrontal gyrus (dmPFG), left precentral gyrus, and left temporoparietal junction in oNC compared to OC women. In OC users, the activity of the left dmPFG and precentral gyrus was negatively associated with behavioral and self-reported affective empathy. Furthermore, empathy-related region-of-interest analysis indicated negative associations of brain activation with synthetic hormone levels in OC women. Overall, this multimodal, cross-sectional investigation of empathy suggests a role of OC intake in especially affective empathy and highlights the importance of including synthetic hormone levels in OC-related analyses.
Diagnostic thresholds and optimal collection protocol of salivary pepsin for gastroesophageal reflux disease
Authors: Ma Steven D , Patel Vandan G , Greytak Madeline , Rubin Joshua E , Kaizer Alexander M , Yadlapati Rena H 
Published: September 2022

Summary
Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver–operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time &lt; 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD.
A systematic review and meta-analyses on the effects of atorvastatin on blood pressure and heart rate
Authors: Costa Gabriel S , Julião-Silva Letícia S , Belo Vinícius S , de Oliveira Helena C F , Chaves Valéria E 
Published: September 2022

Abstract

Aims
Considering the inconsistencies in the literature on the atorvastatin effect on blood pressure (BP), we performed these meta-analyses.

Methods and results
Through a search of the Excerpta Medica Database (EMBASE), PubMed, and Web of Science databases, 1412 articles were identified, from which 33 randomized clinical trials (RCT) and 44 pre-clinical were selected. Populations from RCT were stratified according to baseline BP and lipid levels. We performed meta-analyses of the effect of atorvastatin on systolic (SBP), diastolic and mean BP; heart rate (HR); HR variability, and baroreflex. Atorvastatin reduced SBP in the overall population (P = 0.05 vs. placebo; P = 0.03 vs. baseline), in normotensive and hyperlipidaemic (P = 0.04 vs. placebo; P = 0.0001 vs. baseline) and in hypertensive and hyperlipidaemic (P = 0.02 vs. placebo; P = 0.008 vs. baseline) individuals in parallel RCT, but it did not affect SBP in normotensive and normolipidaemic individuals (P = 0.51 vs. placebo; P = 0.4 vs. baseline). Although an effect of atorvastatin was detected in hyperlipidaemic individuals, the meta-regression coefficient for the association of low density lipoprotein (LDL)-cholesterol reduction with SBP reduction in the overall population demonstrated that SBP reduction is not dependent on the changes in LDL-cholesterol. A meta-analysis of preclinical reports demonstrated that SBP was reduced in atorvastatin-treated hypertensive and normolipidaemic rats (spontaneously hypertensive rats: P &lt; 0.00001), but not in normotensive and normolipidaemic rats (control rats: P = 0.97). Atorvastatin also reduced the HR in spontaneously hypertensive rat.

Conclusion
Atorvastatin lowers BP independent of LDL-cholesterol levels. Additional studies are needed to estimate the involvement of the autonomic nervous system in the BP-lowering effect of atorvastatin.
Albuminuria as a marker of systemic congestion in patients with heart failure
Authors: Boorsma Eva M , ter Maaten Jozine M , Damman Kevin , van Essen Bart J , Zannad Faiez , van Veldhuisen Dirk J , Samani Nilesh J , Dickstein Kenneth , Metra Marco , Filippatos Gerasimos , Lang Chim C , Ng Leong , Anker Stefan D , Cleland John G , Pellicori Pierpaolo , Gansevoort Ron T , Heerspink Hiddo J L , Voors Adriaan A , Emmens Johanna E 
Published: September 2022

Abstract

Aims
Albuminuria is common in patients with heart failure and associated with worse outcomes. The underlying pathophysiological mechanism of albuminuria in heart failure is still incompletely understood. The association of clinical characteristics and biomarker profile with albuminuria in patients with heart failure with both reduced and preserved ejection fractions were evaluated.

Methods and results
Two thousand three hundred and fifteen patients included in the index cohort of BIOSTAT-CHF were evaluated and findings were validated in the independent BIOSTAT-CHF validation cohort (1431 patients). Micro-albuminuria and macro-albuminuria were defined as urinary albumin–creatinine ratio (UACR) &gt;30 mg/gCr and &gt;300 mg/gCr in spot urines, respectively. The prevalence of micro- and macro-albuminuria was 35.4% and 10.0%, respectively. Patients with albuminuria had more severe heart failure, as indicated by inclusion during admission, higher New York Heart Association functional class, more clinical signs and symptoms of congestion, and higher concentrations of biomarkers related to congestion, such as biologically active adrenomedullin, cancer antigen 125, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (all P &lt; 0.001). The presence of albuminuria was associated with increased risk of mortality and heart failure (re)hospitalization in both cohorts. The strongest independent association with log UACR was found for log NT-proBNP (standardized regression coefficient 0.438, 95% confidence interval 0.35–0.53, P &lt; 0.001). Hierarchical clustering analysis demonstrated that UACR clusters with markers of congestion and less with indices of renal function. The validation cohort yielded similar findings.

Conclusion
In patients with new-onset or worsening heart failure, albuminuria is consistently associated with clinical, echocardiographic, and circulating biomarkers of congestion.
Digitally enabled cardiac rehabilitation following coronary revascularization: results from a single centre feasibility study
Authors: Hatch Victoria , Davies William R 
Published: September 2022

Abstract
Wearable activity monitors, together with smartphone-based health and fitness applications (apps), are becoming more accessible and their widespread use provides an additional opportunity for the recording of cardiovascular metrics in patients with cardiovascular disease. The use of selected metrics by cardiac rehabilitation (CR) programmes allows the facilitation of individualized and tailored positive lifestyle changes to patients and places the patient at the centre of their recovery programme. To investigate the role of such devices on outcomes with patients on a CR programme, a cohort/case–control study was conducted. Patients post-myocardial infarction who were treated with either percutaneous coronary intervention or surgical coronary revascularisation at a single centre were invited to use a physical activity monitor linked to a customized app at their initial assessment for the rehabilitation programme. Those who accepted were allocated to the treatment group. The control group was selected from a larger pool of 400 historical and concurrent patients. Propensity matching was used to associate each case with their closest control. The changes in self-reported physical activity were similar for both groups at the end of the CR programme (EOP). The digitally monitored group tended to achieve greater METS (metabolic equivalent of task - a measure of exercise intensity) at 12 weeks (P &lt; 0.059); however, no difference was observed in the overall change in METS at EOP (P &lt; 0.333). Although no difference was noted in diastolic blood pressure, a statistically significant drop in the systolic blood pressure in the digitally monitored group (P &lt; 0.004) was detected. In this study, the innovative combination of technology and face-to-face CR showed promising results and assisted the individualization of delivered content. This intervention could easily be replicated and expanded. Challenges are the recruitment of the elderly population, those who may be less engaged with or have less access to technology, and the underrepresentation of women in the study sample.
The efficacy and safety of a nurse-led electrical cardioversion service for atrial fibrillation over a 2-year time period
Authors: Purkayastha Pujon , Ibrahim Abdalla , Haslen Dawn , Gamma Reto 
Published: September 2022

Abstract

Aims
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide, with a significant impact on morbidity, mortality, and utilization of healthcare resources. Electrical direct-current cardioversion (DCCV) is offered to patients with ongoing symptoms despite medical management. In this study, we aim to evaluate the safety and efficacy of a specialized nurse-led DCCV service.

Methods and results
This was a retrospective cohort study analysing the outcome of patients presenting with AF or flutter, who were subsequently referred for a nurse-led DCCV procedure between August 2017 and December 2019. Analysis included a total of 341 patients (mean age = 68.37; standard deviation = 10.96) who presented with either AF (N = 267; 78.30%) or atrial flutter (N = 74; 21.70%). Approximately 30% of patients were females (N = 101) and 70% were males (N = 240). Of the 341 patients who underwent DCCV, 299 were successfully cardioverted (87.68%). Of those patients successfully cardioverted, 167 remained in sinus rhythm after 6 weeks (55.85%); 93 patients reverted back to AF (31.10%). Thirty-eight patients were lost to follow up (12.71%). Of all 341 patients who underwent DCCV, only 24 patients were admitted to hospital during the subsequent 3-month period (7.04%). Importantly, no patients were admitted as a direct complication of the DCCV procedure.

Conclusion
Overall, data gathered from this study provides positive evidence to support the use of a nurse-led DCCV service. In addition to obtaining very successful cardioversion rates, we found low remission rates, with a very low hospital readmission rate for AF-related issues after successful DCCV.
Does it fit better? Measures of physical activity among adolescents in relation to health indicators
Authors: Karchynskaya Viktoryia , Kopcakova Jaroslava , Madarasova Geckova Andrea , de Winter Andrea F , Reijneveld Sijmen A 
Published: September 2022

Abstract

Background
Measuring physical activity (PA) is one of the pillars of successful health promotion; however, we struggle to find a tool enabling the identification of risk groups. The current standard approach of assessing moderate-to-vigorous physical activity (MVPA) every day does this inadequately. The aim of this study is to explore whether three other indicators of adolescents’ PA can identify such risk groups in a better way.

Methods
We used data on 888 11- to 15-year-old adolescents (mean age = 13.5, 56% boys) from the Health Behaviour in School-aged Children study conducted in 2018 in Slovakia. Sufficient PA was indicated by the following four indicators: (i) MVPA every day, (ii) MVPA 5–7 days a week, (iii) engagement in organized sports (team or individual) and (iv) combining MVPA 5–7 days a week and engagement in organized sports. We used binary logistic regression analysis to assess the association of various indicators of adolescents’ PA with body composition, cardiovascular fitness and self-rated health (SRH), considering age and gender.

Results
Being active based on various indicators was associated with better health outcomes, with the strongest associations for the indicator combining MVPA 5–7 days a week and engagement in organized sports. The only exceptions were the non-significant associations of active adolescents (being active 5–7 days per week or engaged in organized sports) with cardiovascular fitness and SRH.

Conclusions
Measuring PA using an indicator that combines MVPA 5–7 days a week and engagement in organized sports is the most valid using three health indicators as criteria.
Mixed linear and non-linear tree volume models with regional parameters to main tree species in Finland
Authors: Kangas Annika , Pitkänen Timo P , Mehtätalo Lauri , Heikkinen Juha 
Published: September 2022

AbstractThe volume models that have been used in Finland for the last 40 years, while generally well thought-out, exhibit an illogical behaviour for small trees. In recent studies, tree stem form was observed to have changed in time and also involve spatial variation attributable to environmental factors. It is yet unclear how the stem taper has actually changed. To overcome these problems, we fitted a completely new set of volume and taper curve models and examined whether this change is attributable to the changes in management and environmental factors rather than to measurement errors in the previously used datasets. For the latter, we added a dataset into the analysis, which was smaller but of higher quality due to the destructive nature of the stem taper measurements. We aim at (1) developing a new non-linear variable form factor volume function that works with trees of all sizes, (2) improving the description of the variation of the stem form in time and space by including temperature sum and soil type as predictors, (3) understanding the changes in the stem form by fitting new taper curve models and (4) improving the statistical properties of the predictions by using mixed model techniques and by addressing the effect of parameter uncertainty. To assess the impact of renewing the models, we (5) predicted the mean volume and its confidence interval with each model for forest inventory data at country level. The results show that the tree stem form has a spatial trend that can be described with the temperature sum. Moreover, the changes in stem form also have a spatial trend, with largest changes in Lapland. The difference is mostly observable in the lowest part of the stem, and it is especially large in the largest pines. We conclude that environmental variables can help to improve national stem taper functions in countries with pronounced environmental gradients.
The Role of Physical Activity on the Relationships Between Pain, Anxiety, and Sleep Quality in Older Age
Authors: Sheffler Julia L , Saliga Hollyn , Pickett Scott 
Published: September 2022

Abstract

Background
Sleep quality is associated with a range of negative outcomes in older adults, including a higher risk for cognitive decline, greater disability, and poorer quality of life. Pain and anxiety are both important factors associated with poor sleep quality. Physical activity (PA) is frequently recommended to enhance sleep quality and may have additional benefits for pain and anxiety symptoms. However, current models have not examined the interplay among these factors in relation to sleep quality in older adults.

Methods
We examined survey data from a community sample of 281 older adults (aged 55–98 years). Bootstrapped mediation and moderated mediation models using the PROCESS macro in SPSS were used to analyze indirect pathways from pain and anxiety to sleep quality and the conditional effects of exercise.

Results
Higher levels of pain and anxiety were significantly and independently associated with poorer sleep quality in older adults. The effect of pain on sleep quality was partially mediated by anxiety symptoms. PA significantly moderated the effects of anxiety on sleep quality, while it did not significantly impact the relationship between pain and sleep quality. The overall indirect effect was not moderated by PA.

Conclusion
Pain and anxiety are both significant predictors of sleep quality in older adults, and pain influences sleep quality in older adults partially through its influence on anxiety symptoms. PA may be beneficial for sleep quality for individuals with high anxiety, but patients may see fewer benefits from PA if sleep problems are primarily related to pain.
Influence of implementation strategies on implementation outcomes in a statewide dissemination of Faith, Activity, and Nutrition (FAN)
Authors: Saunders Ruth P , Wilcox Sara , Hutto Brent 
Published: September 2022

Abstract
Faith-based organizations are promising settings for implementation science because they can reach populations bearing a disproportionate burden of chronic disease. This study examined how implementation strategies influenced implementation outcomes in Faith, Activity, and Nutrition (FAN) statewide dissemination. Ninety-three (9%) of 985 invited churches enrolled; 91 (98%) and 83 (89%) completed baseline and 12-month assessments. Community Health Advisors trained and provided phone technical assistance to church committees, led by a FAN coordinator. Church committees were charged with developing plans and installing healthy eating (HE) and physical activity (PA) policies, opportunities, messages and pastor support (implementation outcomes). Structural equation modeling examined how implementation strategies influenced implementation outcomes. Nearly all (99%) FAN coordinators and 60% of pastors attended training, 57% of committees submitted program plans and 51%/54% (HE/PA) of committees met ‘every few months’. Statistically significant (P &lt; 0.05) model paths showed positive influences of strategies on implementation outcomes: pastor training on HE and PA pastor support; plan completion on HE and PA messages, PA policies and opportunities as well as FAN committee meetings and committee meetings on HE pastor support, HE policies, PA opportunities and HE and PA messages. This study advances implementation science and provides a model applicable to organizations such as worksites and schools.
Decolonization and Genocide: Re-Examining Indian Partition, 1946–1947
Authors: Jana Sayantani 
Published: September 2022

ABSTRACT
This article proposes that the Indian Partition of 1947 could be classified as a form of “decolonizing genocide.” It draws upon the original Lemkinian criteria for genocide in order to re-examine aspects of Partition violence. The author thus discusses the need to expand the existing terminology and frameworks that scholars have previously used to analyze the Partition; examines the different state and non-state groups involved, and how the climate of decolonization enabled different state and non-state groups to mobilize in various forms and degrees; and studies the victim groups, particularly, women and their experiences of sexual violence. From the case of Indian Partition, this article argues that the conditions present during decolonization help to perpetuate a specific kind of organized violence, carried out by state, quasi-state, and non-state agents, which is genocidal in both its logic and nature. Thus, re-examining Indian Partition as decolonizing genocide allows us to move beyond Eurocentric and state-oriented definitions of genocide in order to create a more effective approach towards understanding mass violence in decolonizing and postcolonial societies.