Methodological Limitations Research Articles

Machine learning applications in sheet metal constitutive Modelling: A review

The numerical simulation of sheet metal forming processes depends on the accuracy of the constitutive model used to represent the mechanical behaviour of the materials. The formulation of these constitutive models, as well as their calibration process, has been an ongoing subject of research. In recent years, there has been a special focus on the application of data-driven techniques, namely Machine Learning, to address some of the difficulties of constitutive modelling. This review explores different methodologies for the application of Machine Learning algorithms to sheet metal constitutive modelling. These methodologies include the use of machine learning algorithms in the identification of constitutive model parameters and the replacement of the constitutive model by a metamodel created by a machine learning algorithm. A discussion about the merits and limitations of the different methodologies is presented, as well as the identification of some possible gaps in the literature that represent opportunities for future research.

Optimizing pervious concrete with machine learning: Predicting permeability and compressive strength using artificial neural networks

This study makes a significant contribution to the field of pervious concrete by using machine learning to innovatively predict both mechanical and hydraulic performance. Unlike existing methods that rely on labor-intensive trial-and-error experiments, our proposed approach leverages a multilayer perceptron network. To develop this approach, we compiled a comprehensive dataset comprising 271 sets and 3,252 experimental data points. Our methodology involved evaluating 22,246 network configurations, employing Monte Carlo cross-validation over 20 iterations, and using 4 training algorithms, resulting in a total of 1,779,680 training iterations. This results in an optimized model that integrates diverse mix design parameters, enabling accurate predictions of permeability and compressive strength even in the absence of experimental data, achieving R² values of 0.97 and 0.98, respectively. Sensitivity analyses validate the model's alignment with established principles of pervious concrete behavior. By demonstrating the efficacy of machine learning as a complementary tool for optimizing pervious concrete mix designs, this research not only addresses current methodological limitations but also lays the groundwork for more efficient and effective approaches in the field.

Does the chairman’s political and royal authority matter? Evidence from ESG disclosure in Gulf Cooperation Council

Purpose This study aims to explore the influence of the chairman’s political and royal authority on environmental, social and governance (ESG) disclosure within the context of nonfinancial companies listed in the Gulf Cooperation Council (GCC). Design/methodology/approach The authors adopt a mixed-methods approach, analyzing a data set of 262 nonfinancial GCC companies from 2016 to 2021. The authors use content analysis to collect the ESG disclosure data based on the ESG Disclosure Guidance provided by the GCC Financial Markets Committee. Quantitative methods are applied to investigate the effect of the chairman’s political and royal authority on ESG disclosure. The credibility of the findings is fortified through rigorous robustness and endogeneity tests. Findings Consistent with the resource-based view and servant leadership theory, the authors found a positive impact of the chairman’s political and royal authority on ESG disclosure. Practical implications The findings of this study insight investors to consider the complex relationship between political affiliations and governance practices to align investments with sustainability and ethical criteria, thereby improving investment strategies in these contexts. This research offers a solid foundation for regulatory craft governance frameworks that acknowledge and incorporate the unique influence of royal family members and politically connected individuals within corporate boards. Originality/value This study enhances the discourse on ESG disclosure by focusing on the underrepresented GCC region. This research breaks new ground by focusing on the impact of the chairman’s political and royal authority on ESG disclosure. In addition, it addresses previous methodological limitations by incorporating more comprehensive ESG data for the GCC market.

The effect of sexual orientation on voice acoustic properties.

Previous research has investigated sexual orientation differences in the acoustic properties of individuals' voices, often theorizing that homosexuals of both sexes would have voice properties mirroring those of heterosexuals of the opposite sex. Findings were mixed, but many of these studies have methodological limitations including small sample sizes, use of recited passages instead of natural speech, or grouping bisexual and homosexual participants together for analyses. To address these shortcomings, the present study examined a wide range of acoustic properties in the natural voices of 142 men and 175 women of varying sexual orientations, with sexual orientation treated as a continuous variable throughout. Homosexual men had less breathy voices (as indicated by a lower harmonics-to-noise ratio) and, contrary to our prediction, a lower voice pitch and narrower pitch range than heterosexual men. Homosexual women had lower F4 formant frequency (vocal tract resonance or so-called overtone) in overall vowel production, and rougher voices (measured via jitter and spectral tilt) than heterosexual women. For those sexual orientation differences that were statistically significant, bisexuals were in-between heterosexuals and homosexuals. No sexual orientation differences were found in formants F1-F3, cepstral peak prominence, shimmer, or speech rate in either sex. Recommendations for future "natural voice" investigations are outlined.

The effectiveness of neck stretching exercises in alleviating neck pain and self-reported disability after thyroidectomy: A systematic review and meta-analysis of clinical trials.

Thyroidectomy can lead to significant challenges such as neck pain, disability, and limited range of motion. Therefore, our objective is to conduct a systematic review and meta-analysis of clinical trials to investigate the clinical effectiveness of neck stretching exercises in alleviating neck pain and self-reported disability immediately after thyroidectomy. We systematically searched PubMed, CENTRAL, Scopus, and Web of Science from inception until July 28th, 2023. We assessed the selected trials for the risk of bias using both the RoB-2 and ROBINS-I tools. Our specific outcomes were the severity of neck pain and self-reported disability after thyroidectomy. The results were synthesized using risk ratio (RR) and standardized mean differences (SMD) with 95% confidence intervals (CI) in a random-effects model using Stata software. Nine clinical trials, comprising five randomized and four non-randomized trials, were included, with a total of 1026 patients. Neck stretching exercises were significantly associated with improved mean pain scores both after 1 week (n = 625 patients, SMD = -2.43, 95% CI [-4.65, -0.22], p = 0.03, I2 = 98%) and 1 month (n = 545 patients, SMD = -4.11, 95% CI [-8.12, -0.11], p = 0.04, I2 = 99%). Similarly, neck stretching exercises were significantly associated with improved mean self-reported disability scores both after 1 week (n = 298 patients, SMD = -0.70, 95% CI [-1.36, -0.04], p = 0.04, I2 = 87%) and 1 month (n = 298 patients, SMD = -0.42, 95% CI [-0.65, -0.19], p = 0.0004, I2 = 0%). The pooled analysis showed heterogeneity (chi-square p < 0.01, I2 > 80%), except for the mean self-reported neck disability score after 1 month, which showed homogeneity (chi-square p > 0.01, I2 = 0%). This systematic review and meta-analysis, involving 1026 patients, revealed the potential benefits of neck stretching exercises in alleviating neck pain and self-reported disability after thyroidectomy. However, further research is required to address methodological limitations, evaluate long-term outcomes, investigate potential moderators (i.e., the duration or intensity of the exercise program), and explore patients' analgesic consumption.

Relationship between playing-related factors and occupational balance in professional violinists.

Playing performance of musicians may affect their occupational balance. The violin is one of the riskiest string instruments for the musculoskeletal health. To show the effect of socio-demographics, playing posture, pain, and functionality on occupational balance in professional violinists in Istanbul. Forty-five violinists aged 29.1±10.6 years were included. The Personal Information Form, the Edinburgh Handedness Inventory, the Wong-Baker Faces Pain Rating Scale, the Disability of Arm, Shoulder and Hand - Sports/Musicians (DASH-SM), the Rapid Upper Limb Assessment, and the 11-item revised version of the Occupational Balance Questionnaire (OBQ11 - T) were used. Spearman correlation analysis was performed to examine the relationship between the variables and occupational balance. The only significant correlation was found between doing regular exercise and occupational balance (r = 0.539, p < 0.001) with those having an exercise habit reporting higher occupational balance scores. The mean pain score of the violinists increased from a pre-performing mean of 1.6±2.3 to a post-performance mean of 3.91±2.4. Musicians indicate that they practice physical exercise regularly. A strong methodological limitation of this study is that variables like exercise were evaluated with a self-reported survey which limited the analysis and so we hardly find any relationships between them. To the best of our knowledge, this is the first study to evaluate the relationship between playing-related factors and occupational balance in violinists. There may be other factors affecting occupational balance in violinists and also in the other musicians. Similar studies are needed in other countries also using different assessments specific to musicians.

Potential Health Benefits of a Diet Rich in Organic Fruit and Vegetables versus a Diet Based on Conventional Produce: A Systematic Review.

Over the past decade, the production and consumption of organic food (OF) have received increasing interest. Scientific studies have shown better quality of organic fruit and vegetables (FV) in terms of nutrients and pesticide contents, but it appears difficult to conclude if there are potentially greater health benefits of these products compared with conventional food (CF). To determine whether the current scientific literature demonstrates that a diet rich in organic FV is healthier than 1 based on conventional produce. A systematic search was conducted using the PubMed and Web of Science databases for articles published between January 2003 and December 2022. Articles were analyzed uniformly by 2 reviewer, using a specific template summary sheet, and scored from 1 to 5. The level of evidence and the quality of studies in humans were assessed using the Jadad score and the French National Authority for Health method. A total of 12 human studies were included. Studies often reported contradictory or even opposite results, with methodological limitations. Only 6 of the 12 studies found significant associations between OF and the health outcomes evaluated. The current data do not enable a firm conclusion about a greater health benefit for a diet rich in FV based on products grown organically compared with conventional farming. There is a paucity of available data and considerable heterogeneity in study designs (participants, exposures, durations, health outcomes, and residual confounding factors). Well-designed interventional studies are required.

Palaeodietary reconstruction of wild and domestic goats using dental microwear texture analysis. A case study from two early Neolithic sites in the southern Levant

ABSTRACT Dental microwear (DMA) is a tool used for the palaeodiet reconstruction of animals in Archaeology. The use of this proxy on domestic ungulates provides valuable information to reconstruct livestock strategies, yet it presents several methodological limitations. Most studies have been carried out using low-magnification DMA and the interpretations often relied on comparisons with databases of extant wild ungulates. In addition, several studies have highlighted challenges in discerning diets in extant domestic caprines. In parallel, dental microwear texture analysis (DMTA) – a quantitative methodology based on 3D micro-texture height maps – has shown better discrimination. In this paper, we explore the capacity to distinguish four different management strategies of domestic goats (Capra hircus) and three species of wild ibexes (Capra nubiana, C. pyrenaica and C. ibex) using DMTA. Results revealed good discrimination among extant domestic goat populations and between wild and domestic goats. This new dataset was subsequently used to characterise the palaeodiet of archaeological goats from two Pre-Pottery Neolithic B sites in the southern Levant. Preliminary findings suggest evidence of human intervention in goats at least during the early 8th millennium BCE. In addition, incorporating various current management strategies has enhanced our understanding of early goat domestication in southern Levant.

Cerebral ischemia biomarkers: Their roles in early diagnosis and prognosis with potential clinical applications

Cerebral ischemia, caused by a disruption in blood supply to the brain, remains a significant cause of morbidity and mortality worldwide. Identifying reliable biomarkers for the early diagnosis and prognosis of cerebral ischemia is crucial for timely intervention and improved patient outcomes. This review aims to provide a comprehensive overview of the current knowledge on cerebral ischemia biomarkers, focusing on their potential role in early detection and prediction of clinical outcomes. Specifically, we discuss the current advances in the field of cerebral ischemia biomarkers, which serve as essential tools for early diagnosis and monitoring of ischemic stroke. We examine several promising biomarkers, including omics data, genetic (FOXF2 and ATP5H), physiological and neuroinflammatory biomarkers, neuroimaging markers, blood-based biomarkers (proteins, microRNAs, and metabolites), and newer modalities such as exosomes, microvesicles, and cell-free deoxyribonucleic acid (cfDNA). In addition, we highlight the challenges and future directions in translating these biomarkers into clinical practice. Standardization and reproducibility, methodological limitations, and cost and accessibility are critical challenges in the translation of biomarkers into clinical practice. Addressing these challenges requires multi-stakeholder collaborations and coordinated efforts to establish standardized protocols, improve analytical methods, and develop cost-effective biomarker assays. The use of point-of-care testing devices or miniaturized lab-on-a-chip technologies can reduce costs and improve accessibility, particularly in low-resource settings. Furthermore, collaborations between academia, industry, and regulatory agencies can facilitate the translation of biomarkers by addressing regulatory and reimbursement hurdles that affect the affordability and availability of these tests.

A Scoping Review on the Effects of Kinesio Taping on Oropharyngeal Function Related to Swallowing and Feeding.

Following the expansion of interdisciplinary communication among rehabilitative service providers, new techniques have been introduced for treating swallowing disorders. Kinesio taping (KT) is one of the recently noticed techniques in the rehabilitation of swallowing and feeding disorders. Given the novelty of this technique in research and practice, the present scoping review aimed to summarize the available evidence on the effects of KT on the oropharyngeal function related to swallowing, and to identify current knowledge gaps to guide future studies. The initial comprehensive search was conducted in the six databases in November 2022 and then was updated in June 2023. Studies were independently reviewed by two authors to exclude all types of reviews and study protocols, studies published only in an abstract form and also studies that used KT for improving voice and dysarthria symptoms. The methodology of the included studies was also critically appraised using Joanna Briggs Institute (JBI) standard tools by two authors. The results of the studies were categorized and reported based on their overall objectives. In final analysis, 21 articles were described. Study designs ranged from randomized control trials (RCTs) to the case reports. The effects of KT had been investigated on drooling, oral feeding skills of infants, immediate activation of swallowing muscles, and management of dysphagia in patients with stroke or cerebral palsy (CP). Although innovative approaches to use KT as a therapeutic method in swallowing disorders have been investigated in the studies, there are many methodological limitations that affected validity of the results. In general, it seems there is not enough evidence to add KT to the usual management of feeding and swallowing disorders yet. Further studies, therefore, are required to achieve more accurate conclusions in each of the objectives summarized in this study.

Professional architects’ design trade-offs in reinforcement learning-powered agent-based simulation

While emphasising play-based approaches in early childhood education, there is a deficiency in the practical understanding of play integration into children’s learning environment design. To support methodological limitations, this study developed a play behaviour model using reinforcement learning agents to generate children’s unpredictable behavioural responses during physical and social play, including unforeseen injuries. In comparative laboratory experiments, 14 professional architects engaged in design tasks before and after using the simulation. The design results were assessed through external expert evaluations, with a focus on the optimal trade-offs between facilitating play behaviours while ensuring safety considerations and on the level of effective design decision making and completeness. The statistical analysis demonstrated that the simulation facilitated optimal trade-offs, enhanced decision making and improved the overall completeness of children’s learning environment design. This research addressed the capabilities of simulation to support a child-centric design, with potential implications for improving early childhood education environments.

Exercise and Smoking Cessation.

Smoking is a public health crisis, leading to a multitude of health complications. Exercise is associated with numerous health benefits and is accepted by health professionals and smokers as a potentially effective smoking cessation aid. This chapter discusses the extant literature on the relation between exercise and smoking, including cross-sectional studies, experiments, and randomized clinical trials. There is robust evidence for exercise's efficacy in reducing cigarette craving, tobacco withdrawal symptoms, and negative affect. Further, exercise-based interventions appear to boost short-term abstinence yet may fall short of facilitating long-term abstinence. Methodological limitations of extant work are reviewed. We conclude with a discussion of the next steps in this line of work to fine-tune exercise interventions and their application for smoking cessation.

More allogrooming is followed by higher physiological stress in wild female baboons.

Social bonds increase fitness in a range of mammals. One pathway by which social bonds may increase fitness is by reducing the exposure to physiological stress, i.e. glucocorticoid (GC) hormones, that can be detrimental to health and survival. This is achieved through downregulating hypothalamic-pituitary-adrenal (HPA)-axis activity. Indeed, long-term measures of social (grooming) bonds are often negatively correlated with HPA-axis activity. However, the proximate role of physical touch through allogrooming remains an open question in the sociality-health-fitness debate. Demonstrating the potential anxiolytic benefits of grooming in the wild is hindered by methodological limitations. Here, we match accelerometer-identified grooming in wild female chacma baboons (Papio ursinus) to non-invasive faecal GC metabolite concentrations (fGCs). Consistent with previous work, we found a negative (but statistically non-significant) overall relationship between individual averaged fGCs and grooming rates. However, when time-matching grooming to fGCs, we found that both more giving and receiving grooming were followed by higher fGCs. This upregulation of HPA-axis activity suggests that maintaining social bonds (and its ultimate fitness benefits) may come at a shorter-term physiological cost. This finding sheds new light on a ubiquitous social behaviour typically considered 'relaxing' and suggests that sociopositive contact can trigger physiological stress.

Meibography signal intensity as a novel image biomarker for meibomian gland function: evidence from cross-sectional and longitudinal analyses.

Meibomian gland dysfunction (MGD), one of the most common ocular surface diseases, can induce dry eye and reduce patients' quality of life. Methodological limitations have resulted in contradictory interpretations of gland function. This study sought to investigate the correlation between meibography signal intensity (SI) and meibomian gland (MG) function and to validate an MGD classification strategy based on different levels of SI. A multicenter, cross-sectional analysis was conducted on 817 eyes from 361 patients with MGD and 52 healthy controls. Additionally, 78 eyes from 39 patients with MGD who had undergone LipiFlow treatment were recruited for longitudinal analyses. The SI value was obtained via meibography using an automated analyzer, and all participants underwent ocular surface examinations. A cross-sectional analysis was performed to determine SI distribution and its relationship to clinical characteristics via a generalized estimating equation model. Longitudinal analyses were conducted on the treatment cohort using a mixed-effects model to explore the outcome in different SI levels. Regression analysis revealed significant correlations between SI and lipid layer thickness (β=0.016), meibum expressibility (β=-0.676), meibum quality (β=-0.251), and fluorescein-stained tear-film break-up time (FBUT) (β=0.064) (all P values <0.001 for the above associations). Low-level SI MGD cases exhibited the most severe clinical signs, including the worst meibum expressibility (16% for level 3) and quality scores (19% for level 3), the shortest FBUT (3.82±0.13 s), and the thinnest lipid layer (65.68±2.58 nm), (all P values <0.05, respectively). Patients with medium SI showed the lowest ocular surface disease index (OSDI) value (26.64±1.06), the longest FBUT (4.56±0.08 s), and the thickest lipid layer (80.20±2.90 nm). After treatment, the high SI values reduced significantly at each follow-up point compared to baseline (all P values <0.05). The medium SI group demonstrated the greatest improvement in symptoms and signs, followed by the high SI group, and the low SI group. Automated measurements of SI can effectively reflect MG secretory activity. The proposed low, medium, and high SI classifications represent different functional subtypes of MGD.

Drusen in the macula and parapapillary region.

To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in the parapapillary region. We histomorphometrically examined human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. The study included 106 eyes (age, 62.6 ± 15.2years) with macular drusen (n = 7 globes) or parapapillary drusen (n = 29 eyes) and 70 eyes without drusen. In all drusen, periodic-acid-Schiff-positive material was located between the RPE basal membrane and the inner collagenous layer of Bruch's membrane (BM). Macular drusen as compared with parapapillary drusen had lower height (15.2 ± 10.1µm versus 34.3 ± 19.8µm; P = 0.003), while both groups did not differ significantly in basal drusen width (74.0 ± 36.3µm versus 108.7 ± 101.0µm; P = 0.95). Eyes with macular drusen and eyes without drusen did not differ significantly in BM thickness (2.74 ± 0.44µm versus 2.55 ± 0.88µm; P = 0.57) or in RPE cell density (35.4 ± 10.4 cells/480µm versus 32.8 ± 7.5 cells/480µm; P = 0.53), neither in the drusen region nor in the drusen vicinity, while BM thickness (4.60 ± 1.490µm; P < 0.001) and RPE cell density (56.9 ± 26.8 cells/480µm; P = 0.005) were higher at the parapapillary drusen. Eyes with macular drusen, eyes with parapapillary drusen, and eyes without drusen did not differ significantly in choriocapillaris density (all P > 0.10) and thickness (all P > 0.35). Limitations of the study, among others, were a small number and size of drusen examined, diseases leading to enucleation, lack of serial sections, limited resolution of light microscopy, and enucleation-related and histological preparation-associated artefacts. The findings of this study, also taking into account its methodological limitations, suggest that macular drusen and parapapillary drusen shared the morphological feature of periodic-acid-Schiff-positive material between the RPE basal membrane and BM and that they did not vary significantly in choriocapillaris thickness and density. RPE cell density and BM thickness were higher in parapapillary drusen than in macular drusen.

RNA polymerases reshape chromatin architecture and couple transcription on individual fibers

RNA polymerases must initiate and pause within a complex chromatin environment, surrounded by nucleosomes and other transcriptional machinery. This environment creates a spatial arrangement along individual chromatin fibers ripe for both competition and coordination, yet these relationships remain largely unknown owing to the inherent limitations of traditional structural and sequencing methodologies. To address this, we employed long-read chromatin fiber sequencing (Fiber-seq) in Drosophila to visualize RNA polymerase (Pol) within its native chromatin context with single-molecule precision along up to 30 kb fibers. We demonstrate that Fiber-seq enables the identification of individual Pol II, nucleosome, and transcription factor footprints, revealing Pol II pausing-driven destabilization of downstream nucleosomes. Furthermore, we demonstrate pervasive direct distance-dependent transcriptional coupling between nearby Pol II genes, Pol III genes, and transcribed enhancers, modulated by local chromatin architecture. Overall, transcription initiation reshapes surrounding nucleosome architecture and couples nearby transcriptional machinery along individual chromatin fibers.

Novel insights on microbiome dynamics during a gill disease outbreak in farmed rainbow trout (Oncorhynchus mykiss)

The generic term “Gill disease” refers to a wide range of disorders that affect the gills and severely impact salmonid aquaculture systems worldwide. In rainbow trout freshwater aquaculture, various etiological agents causing gill diseases have been described, particularly Flavobacterium and Amoeba species, but research studies suggest a more complex and multifactorial aetiology. Here, a cohort of rainbow trout affected by gill disease is monitored both through standard laboratory techniques and 16S rRNA Next-Generation Sequencing (NGS) analysis during a natural disease outbreak and subsequent antibiotic treatment with Oxytetracycline. NGS results show a clear clustering of the samples between pre- and post-treatment based on the microbial community of the gills. Interestingly, the three main pathogenic bacteria species in rainbow trout (Yersinia ruckeri, Flavobacterium psychrophilum, and Flavobacterium branchiophilum) appear to be weak descriptors of the diversity between pre-treatment and post-treatment groups. In this study, the dynamics of the gill microbiome during the outbreak and subsequent treatment are far more complex than previously reported in the literature, and environmental factors seem of the utmost importance in determining gill disease. These findings present a potential novel perspective on the diagnosis and management of gill diseases, showing the limitations of conventional laboratory methodologies in elucidating the complexity of this disease in rainbow trout. To the authors’ knowledge, this work is the first to describe the microbiome of rainbow trout gills during a natural outbreak and subsequent antibiotic treatment. The results of this study suggest that NGS can play a critical role in the analysis and comprehension of gill pathology. Using NGS in future research is highly recommended to gain deeper insights into such diseases correlating gill’s microbiome with other possible cofactors and establish strong prevention guidelines.

Comparison of oral anticoagulants for stroke prevention in atrial fibrillation using the UK clinical practice research Datalink Aurum: A reference trial (ARISTOTLE) emulation study.

Stroke prevention guidance for patients with atrial fibrillation (AF) uses evidence generated from randomised controlled trials (RCTs). However, applicability to patient groups excluded from trials remains unknown. Real-world patient data provide an opportunity to evaluate outcomes in a trial analogous population of direct oral anticoagulants (DOACs) users and in patients otherwise excluded from RCTs; however, there remains uncertainty on the validity of methods and suitability of the data. Successful reference trial emulation can support the generation of evidence around treatment effects in groups excluded or underrepresented in trials. We used linked United Kingdom primary care data to investigate whether we could emulate the pivotal ARISTOTLE trial (apixaban versus warfarin) and extend the analysis to investigate the impact of warfarin time in therapeutic range (TTR) on results. Patients with AF in the UK Clinical Practice Research Datalink (CPRD Aurum) prescribed apixaban or warfarin from 1 January 2013 to 31 July 2019 were selected. ARISTOTLE eligibility criteria were applied to this population and matched to the RCT apixaban arm on baseline characteristics creating a trial-analogous apixaban cohort; this was propensity-score matched to warfarin users in the CPRD Aurum. ARISTOTLE outcomes were assessed using Cox proportional hazards regression stratified by prior warfarin exposure status during 2.5 years of patient follow-up and results benchmarked against the trial results before treatment effectiveness was further evaluated based on (warfarin) TTR. The dataset comprised 8,734 apixaban users and propensity-score matched 8,734 warfarin users. Results [hazard ratio (95% confidence interval)] confirmed apixaban noninferiority for stroke or systemic embolism (SE) [CPRD 0.98 (0.82,1.19) versus trial 0.79 (0.66,0.95)] and death from any cause [CPRD 1.03 (0.93,1.14) versus trial 0.89 (0.80,0.998)] but did not indicate apixaban superiority. Absolute event rates for stroke/SE were similar for apixaban in CPRD Aurum and ARISTOTLE (1.27%/year), whereas a lower event rate was observed for warfarin (CPRD Aurum 1.29%/year, ARISTOTLE 1.60%/year). Analysis by TTR suggested similar effectiveness of apixaban compared with poorly controlled warfarin (TTR < 0.75) for stroke/SE [0.91 (0.73, 1.14)], all-cause death [0.94 (0.84, 1.06)], and superiority for major bleeding [0.74 (0.63, 0.86)]. However, when compared with well-controlled warfarin (TTR ≥ 0.75), apixaban was associated with an increased hazard for all-cause death [1.20 (1.04, 1.37)], and there was no significant benefit for major bleeding [1.08 (0.90, 1.30)]. The main limitation of the study's methodology are the risk of residual confounding, channelling bias and attrition bias in the warfarin arm, and selection bias and misclassification in the analysis by TTR. Analysis of noninterventional data generated results demonstrating noninferiority of apixaban versus warfarin consistent with prespecified benchmarking criteria. Unlike in ARISTOTLE, superiority of apixaban versus warfarin was not seen, possible due to the lower proportion of Asian patients and higher proportion of patients with well-controlled warfarin compared to ARISTOTLE. This methodological template can be used to investigate treatment effects of oral anticoagulants in patient groups excluded from or underrepresented in trials and provides a framework that can be adapted to investigate treatment effects for other conditions.

Balancing Donor Health and Plasma Collection: A Systematic Review of the Impact of Plasmapheresis Frequency

Most plasma used for manufacturing plasma-derived medicinal products (PDMPs) such as albumin, immunoglobulin (Ig), and clotting factors is obtained from source plasma collected via plasmapheresis, the majority of which is contributed by the United States (US). While the demand for PDMPs continues to rise, it remains unclear whether high-frequency plasmapheresis, such as the twice-weekly plasma donation allowed in the US, may have any (long-term) adverse health effects on the donor. To investigate the frequency at which plasma can be donated without harm to the donor, the current systematic review explores the impact of plasma donation frequency on cardiovascular health, protein depletion, and adverse events in healthy plasma donors. We asked the following research question: What is the impact of plasmapheresis frequency (Intervention) on the safety or health (Outcome) of healthy donors (Population)? Six databases (PubMed, Embase, Web of Science, CINAHL, the Cochrane Library, and Transfusion Evidence Library), 2 clinical trial registries (ICTRP and clinicaltrials.gov), and the PROSPERO database were searched. Four observational and 2 experimental studies were included. The results showed that very high-frequency donation (twice per week) may result in a clinically relevant decrease in ferritin and bring IgG levels below the lower threshold of 6 g/l. However, the evidence is of low to very low certainty, and solid conclusions are hindered by the healthy donor effect and methodological limitations of the included studies. To determine a safe threshold donation frequency that minimizes any possible harmful effect on the donor, more high-quality prospective cohort studies and experimental studies are needed. We should expedite such studies to support recommendations, as conclusive evidence confirming or refuting the safety of maximum allowed donation frequencies is lacking. Donor protection is essential, given that healthy donors receive no direct medical benefit from donating plasma.

Implant Treatment in Patients With Autoimmune Diseases: A Systematic Review and Analysis of Studies.

Dental implants provide a reliable solution for edentulous patients with autoimmune diseases improving quality of life. The present systematic review aimed to determine whether autoimmune diseases with oral manifestations could affect the survival rate of dental implants. A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), using Google Scholar and PubMed electronic databases, between the year 2000 and February 2024. The eligibility criteria included human studies, in English language reporting on patients with autoimmune diseases treated with dental implants. Nineteen studies were included: nine on oral lichen planus (OLP), four on Sjögren's syndrome (SS), five on epidermolysis bullosa (EB), and one on lupus erythematosus (LE). A total of 389 implants in 142 patients with OLP showed a survival rate (SR) of 94.6%, while 316 implants in 111 patients with SS had a survival rate of 95.8%. In 31 patients with EB, 181 implants were placed with a survival rate of 99.5%, and 12 implants were placed in five patients with LE with a survival rate of 100% after one year of function. Despite the heterogeneity and methodological limitations of most of the studies, the results showed that dental implant survival rates were comparable to those reported in the general population. This review suggested that dental implants are a viable treatment option for patients with autoimmune diseases. Nevertheless, proper daily oral hygiene and long-term follow-up are decisive factors for the long-term maintenance of dental implants.