Hasil untuk "Medicine (General)"

Anastasia Lam, Yana C Vierboom, Jessica S West

Background Objective measurements estimated that 1.57 billion people globally had hearing loss in 2019. However, where audiologists are sparse, self-reported measures have been suggested as alternatives to assess burden. Moreover, research suggests this number varies by gender, due to biological and social mechanisms. Further refining our knowledge of the global prevalence of hearing loss will provide better understanding of which groups are most affected and how to best allocate resources.Methods Using Gateway to Global Ageing data and the South African National Income Dynamics Study, we estimated the prevalence and men:women ratio of self-reported hearing loss and hearing aid use for 28 countries. Hearing loss was measured as having fair/poor hearing or reporting hearing aid use. We included 664 580 observations of individuals aged 50+ years.Results We found that the four countries with the highest levels of hearing loss (China 65%, South Korea 39%, Mexico 33%, Brazil 31%) also had the lowest reported hearing aid use (as low as 1% in China). Though men were more likely than women to report hearing loss in nearly all countries, especially in regions with higher hearing aid use (USA, Northern/Western Europe), China, South Korea and South Africa reported no gender difference. As the prevalence of hearing loss and hearing aid use increased with age, gender differences generally decreased.Conclusion International variation underscores the importance of country context in shaping perceived hearing and hearing aid use. Regions with high levels of hearing loss and low hearing aid use may be especially amenable to interventions.

Giacomo Buso, Thomas Weber, Christos Fragoulis et al.

Background Acute blood pressure (BP) elevations are common in emergency settings and are traditionally classified into hypertensive urgencies (HU) and hypertensive emergencies (HE). Malignant hypertension (MHT) represents a severe form of HE characterised by small vessel damage. Although international guidelines provide clear definitions and treatment strategies, real-world data have shown persistent fragmentation and heterogeneity in the diagnosis and management of these patients.Methods A web-based, anonymous survey promoted by the European Society of Hypertension (ESH) was distributed among physicians from 18 European and 4 non-European countries. The questionnaire assessed definitions, diagnostic work-up, BP measurement practices, and therapeutic strategies for HU, HE, and MHT.Results Sixty–four participants in 56 centres completed the survey. HU was correctly defined as a severe BP elevation without acute clinically symptomatic hypertension-mediated organ damage (A-HMOD) by 45.3% of respondents. Small cuffs were available to 79.7% and extra-large cuffs to 70.3% of respondents.. Intravenous antihypertensive therapy was used for HE by 88.7% of participants, while 20.6% also used intravenous drugs for HU. Parenteral clonidine and sublingual nifedipine were prescribed by 29.7% and 26.6% of respondents, respectively. Definitions and therapeutic approaches for MHT varied substantially, with 62.9% adopting a recently proposed definition involving at least three target organ damages in patients with BP >200/120 mmHg.Conclusions This international survey highlights considerable variability in the definition, diagnostic work-up, and therapeutic management of acute BP elevations, emphasising the need for harmonised protocols and further education.

Konstantinos Sechidis, Cong Zhang, Sophie Sun et al.

Assessing treatment effect heterogeneity (TEH) in clinical trials is crucial, as it provides insights into the variability of treatment responses among patients, influencing important decisions related to drug development. Furthermore, it can lead to personalized medicine by tailoring treatments to individual patient characteristics. This paper introduces novel methodologies for assessing treatment effects using the individual treatment effect as a basis. To estimate this effect, we use a Double Robust (DR) learner to infer a pseudo-outcome that reflects the causal contrast. This pseudo-outcome is then used to perform three objectives: (1) a global test for heterogeneity, (2) ranking covariates based on their influence on effect modification, and (3) providing estimates of the individualized treatment effect. We compare our DR-learner with various alternatives and competing methods in a simulation study, and also use it to assess heterogeneity in a pooled analysis of five Phase III trials in psoriatic arthritis. By integrating these methods with the recently proposed WATCH workflow (Workflow to Assess Treatment Effect Heterogeneity in Drug Development for Clinical Trial Sponsors), we provide a robust framework for analyzing TEH, offering insights that enable more informed decision-making in this challenging area.

Théo Sourget, Michelle Hestbek-Møller, Amelia Jiménez-Sánchez et al.

The development of larger models for medical image analysis has led to increased performance. However, it also affected our ability to explain and validate model decisions. Models can use non-relevant parts of images, also called spurious correlations or shortcuts, to obtain high performance on benchmark datasets but fail in real-world scenarios. In this work, we challenge the capacity of convolutional neural networks (CNN) to classify chest X-rays and eye fundus images while masking out clinically relevant parts of the image. We show that all models trained on the PadChest dataset, irrespective of the masking strategy, are able to obtain an Area Under the Curve (AUC) above random. Moreover, the models trained on full images obtain good performance on images without the region of interest (ROI), even superior to the one obtained on images only containing the ROI. We also reveal a possible spurious correlation in the Chaksu dataset while the performances are more aligned with the expectation of an unbiased model. We go beyond the performance analysis with the usage of the explainability method SHAP and the analysis of embeddings. We asked a radiology resident to interpret chest X-rays under different masking to complement our findings with clinical knowledge. Our code is available at https://github.com/TheoSourget/MMC_Masking and https://github.com/TheoSourget/MMC_Masking_EyeFundus

Younes Boulaguiem, Luca Insolia, Maria-Pia Victoria-Feser et al.

Multivariate (average) equivalence testing is widely used to assess whether the means of two conditions of interest are `equivalent' for different outcomes simultaneously. The multivariate Two One-Sided Tests (TOST) procedure is typically used in this context by checking if, outcome by outcome, the marginal $100(1-2α$)\% confidence intervals for the difference in means between the two conditions of interest lie within pre-defined lower and upper equivalence limits. This procedure, known to be conservative in the univariate case, leads to a rapid power loss when the number of outcomes increases, especially when one or more outcome variances are relatively large. In this work, we propose a finite-sample adjustment for this procedure, the multivariate $α$-TOST, that consists in a correction of $α$, the significance level, taking the (arbitrary) dependence between the outcomes of interest into account and making it uniformly more powerful than the conventional multivariate TOST. We present an iterative algorithm allowing to efficiently define $α^{\star}$, the corrected significance level, a task that proves challenging in the multivariate setting due to the inter-relationship between $α^{\star}$ and the sets of values belonging to the null hypothesis space and defining the test size. We study the operating characteristics of the multivariate $α$-TOST both theoretically and via an extensive simulation study considering cases relevant for real-world analyses -- i.e.,~relatively small sample sizes, unknown and heterogeneous variances, and different correlation structures -- and show the superior finite-sample properties of the multivariate $α$-TOST compared to its conventional counterpart. We finally re-visit a case study on ticlopidine hydrochloride and compare both methods when simultaneously assessing bioequivalence for multiple pharmacokinetic parameters.

Kinga Skieresz-Szewczyk, Hanna Jackowiak

Connexins are important proteins involved in cell-to-cell communication and cytodifferentiation during renewal and cornification of the multilayered epithelia. So far, there is a lack of reports on this subject in birds’ structurally different ortho- and parakeratinized epithelium of the tongue. The study aims to describe the distribution and expression profiles of the α-connexins (Cx40 and 43) and β-connexins (Cx26, 30, and 31) in those epithelia in duck, goose, and domestic turkey. Research revealed the presence of the mentioned connexins and the occurrence of interspecies differences. Connexins form gap junctions in the cell membrane or are in the cytoplasm of keratinocytes. Differences in connexin expression were noted between the basal and intermediate layers, which may determine the proliferation of keratinocytes. Cx40, 43, and Cx30 in the gap junction of the keratinocytes of the intermediate layer are related to the synchronization of the cornification process. Because of the exfoliation of cornified plaques, a lack of connexins was observed in the cornified layer of orthokeratinized epithelium. However, in parakeratinized epithelium, connexins were present in the cell membrane of keratinocytes and thus maintained cellular integrity in gradually desquamating cells. The current studies will be useful in further comparative analyses of normal and pathological epithelia of the oral cavity in birds.

Claudia S. Priglinger, Günter Rudolph, Irene Schmid et al.

Abstract Background Biallelic pathogenic variants in the neuroblastoma‐amplified sequence (NBAS) gene manifest in a broad spectrum of disorders, including, but not limited to recurrent acute liver failure, skeletal dysmorphism, susceptibility to infections, and SOPH syndrome with its cardinal symptoms of short stature, optic atrophy, and Pelger–Huët anomaly. We aimed to present clinical and genetic characteristics of two sisters (20 and 15 years old) who were diagnosed with optic atrophy and cone dystrophy in childhood. Genome sequencing revealed two novel variants in NBAS in compound heterozygous state in both sisters, namely a 1‐bp deletion predicted to result in a premature termination codon (c.5104del; p.(Met1702*)), and a non‐canonical splice site variant of unclear significance (c.886‐5T>A; p.?). Results Clinical examination and history revealed cone dystrophy, optic atrophy, and Pelger–Huët anomaly, but no short stature, recurrent acute liver failure, or susceptibility to infections. RNA analysis revealed that the c.886‐5T>A variant results in two aberrant transcripts that are predicted to lead to in frame amino acid changes in the β‐propeller region of the protein. Conclusion We hypothesize that the phenotype of our subjects, which appears to be at the end of the spectrum of NBAS‐related disorders, could be explained by residual protein function mediated by the non‐canonical splice site variant c.886‐5T>A. Our study contributes to the existing knowledge on the genotypic and phenotypic spectrum of NBAS‐related disorders.

Farukh Gulzar Khawaja, Khalid Mahmood, Uzma Javed Gul et al.

Objective: To compare Sublay and Onlay mesh repair in terms of post-operative complications among patients undergoing hernioplasty. Study Design: Prospective comparative study. Place and Duration of Study: Surgical Department, Combined Military Hospital, Rawalpindi Pakistan, from Jan 2020 to Jun 2021. Methodology: This study was conducted on 300 patients who underwent hernioplasty for anterior abdominal wall hernias at our hospital. They were randomly divided into two groups before the surgery. Group-A received only mesh repair, while Group-B received subway repair. They were followed up for two weeks for any post-operative complications. Post-operative pain, seroma formation, hematoma formation and the presence of surgical site infection were compared in both groups. Results: Out of 300 patients included in the final analysis, 189(63%) were male, and 111(37%) were female. About 163(54.4%) underwent subway repair, while 137(45.6%) underwent only repair. The commonest complication observed in patients was post-operative pain 68(22.7%), followed by surgical site infection 36(12%). Statistical analysis revealed that seroma formation, post-operative pain and surgical site infection were significantly observed more in patients undergoing only mesh repair than subway repair (p-value<0.05). Conclusion: Post-surgical complications were commonly observed in patients within two weeks of surgery. In addition, patients undergoing Onlay mesh repair were more prone to have seroma formation, post-operative pain and surgical site infection than those undergoing Sublay repair.

Klaudiusz Czudek

Fix an irrational number $α$ and a real function $\mathfrak{p}$ on the circle with $0<\mathfrak{p}<1$. If a particle is placed at a point $x\in \mathbb R/\mathbb Z$, then in the next step it jumps to $x+α$ with probability $\mathfrak{p}(x)$ and to $x-α$ with probability $1-\mathfrak{p}(x)$. Sinai and Kaloshin proved that if $\mathfrak{p}$ is smooth then the random walk is uniquely ergodic and mixing, unless $α$ is Liouville and $\mathfrak{p}$ is symmetric. Unique ergodicity in the general case has been obtained by Conze and Guivarc'h. Here we give an alternative proof of the latter as well as some generic result about mixing, which partially solves a recent open problem.

Finn Behrendt, Debayan Bhattacharya, Robin Mieling et al.

The application of supervised models to clinical screening tasks is challenging due to the need for annotated data for each considered pathology. Unsupervised Anomaly Detection (UAD) is an alternative approach that aims to identify any anomaly as an outlier from a healthy training distribution. A prevalent strategy for UAD in brain MRI involves using generative models to learn the reconstruction of healthy brain anatomy for a given input image. As these models should fail to reconstruct unhealthy structures, the reconstruction errors indicate anomalies. However, a significant challenge is to balance the accurate reconstruction of healthy anatomy and the undesired replication of abnormal structures. While diffusion models have shown promising results with detailed and accurate reconstructions, they face challenges in preserving intensity characteristics, resulting in false positives. We propose conditioning the denoising process of diffusion models with additional information derived from a latent representation of the input image. We demonstrate that this conditioning allows for accurate and local adaptation to the general input intensity distribution while avoiding the replication of unhealthy structures. We compare the novel approach to different state-of-the-art methods and for different data sets. Our results show substantial improvements in the segmentation performance, with the Dice score improved by 11.9%, 20.0%, and 44.6%, for the BraTS, ATLAS and MSLUB data sets, respectively, while maintaining competitive performance on the WMH data set. Furthermore, our results indicate effective domain adaptation across different MRI acquisitions and simulated contrasts, an important attribute for general anomaly detection methods. The code for our work is available at https://github.com/FinnBehrendt/Conditioned-Diffusion-Models-UAD

Alfredo Borgia, Raffaele Raimondi, Tania Sorrentino et al.

The purpose of this study was to summarize the results related to ocular biometry performed using swept-source optical coherence tomography (SS-OCT). A literature search was conducted to search articles reporting the clinical outcomes of patients who underwent examinations with commercially available SS-OCT machines. The available data were thoroughly analyzed, with a particular focus on all the biometric factors used to calculate the power of intraocular lenses (IOLs) implanted during cataract surgery. The agreement, repeatability, and reproducibility of several parameters among different devices were examined. The variations found for parameters obtained from agreement testing were evaluated in order to promote the interchangeability of devices. Swept-source optical coherence tomography biometers usually produce highly repeatable and reproducible results. The excellent results obtained led us to the conclusion that optical biometers based on SS-OCT technology will probably take the lead in ocular biometry.

Hui Xiao, Ion Grama, Quansheng Liu

Let $(g_n)_{n\geq 1}$ be a sequence of independent and identically distributed random elements with law $μ$ on the general linear group $\textup{GL}(V)$, where $V=\mathbb R^d$. Consider the random walk $G_n : = g_n \ldots g_1$, $n \geq 1$. Under suitable conditions on $μ$, we establish the first-order Edgeworth expansion for the coefficients $\langle f, G_n v \rangle$ with $v \in V$ and $f \in V^*$, in which a new additional term appears compared to the case of vector norm $\|G_n v\|$.

G. Tu, Youxia Liao, Qing-Yun Li et al.

Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of ICU/Emergency, Wuhan Third Hospital, Wuhan University, Wuhan 430074, China; Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China These authors contributed equally to this work. Correspondence to: Rui-Lan Wang. Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, Shanghai 201600, China. Email: wangyusun@hotmail.com; Shou-Zhi Fu. Department of ICU/Emergency, Wuhan Third Hospital, Wuhan University, Wuhan 430074, China. Email: fszfsz188@163.com.

Nicholas Chedid, Swalpa Udit, Z. Solhjou et al.

Internal Medicine Residency Program, Brigham andWomen’s Hospital and Harvard Medical SchoolBoston, MA, USA; Department of Medicine, BrighamandWomen’s Hospital and HarvardMedical SchoolBoston,MA, USA; Division of Infectious Diseases, BrighamandWomen’s Hospital and Harvard Medical SchoolBoston, MA, USA; Renal Division, Brigham andWomen’s Hospital and Harvard Medical SchoolBoston, MA, USA; Hospital Medicine Unit and the Division of General Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School Boston, MA, USA.

J. C. P. Leendertse, J. C. P. Leendertse, A. I. Wierdsma et al.

Background: Personal recovery (PR) is a subjective, multidimensional concept, and quantitative research using PR as an outcome is rapidly increasing. This systematic review is intended to support the design of interventions that contribute to PR in psychotic disorders, by providing an overview of associated factors and their weighted importance to PR: clinical factors, social factors, and socio-demographic characteristics are included, and factors related to the concept of PR (organized into CHIME dimensions).Methods: A systematic literature search was conducted from inception to March 2020. Quantitative studies that had used a validated questionnaire assessing the concept of PR were included. Mean effect sizes for the relationship between PR-scale total scores and related factors were calculated using meta-analyses. Sources of heterogeneity were examined using meta-regression tests.Results: Forty-six studies, that used (a total of) eight PR measures, showed that in clinical factors, affective symptoms had a medium negative association with PR-scale total scores (r = −0.44, 95%CI −0.50 to −0.37), while positive, negative and general symptoms had small negative correlations. No association was found with neuro-cognition. Social factors (support, work and housing, and functioning) showed small positive correlations. Gender and age differences had barely been researched. Large associations were found for PR-scale total scores with the CHIME dimensions hope (r = 0.56, 95%CI 0.48–0.63), meaning in life (r = 0.48, 95%CI 0.38–0.58) and empowerment (r = 0.53, 95%CI 0.42–0.63); while medium associations were found with connectedness (r = 0.34, 95%CI 0.43–0.65) and identity (r = 0.43, 95%CI 0.35–0.50). Levels of heterogeneity were high, sources included: the variety of PR measures, variations in sample characteristics, publication bias, variations in outcome measures, and cultural differences.Discussion: Most interventions in mental healthcare aim to reduce symptoms and improve functioning. With regard to stimulating PR, these interventions may benefit from also focusing on enhancing hope, empowerment, and meaning in life. The strength of these findings is limited by the challenges of comparing separate CHIME dimensions with questionnaires assessing the concept of PR, and by the high levels of heterogeneity observed. Future research should focus on the interaction between elements of PR and clinical and social factors over time.

Aria Darbandi, Christina Chopra

Background: Gallbladder disease confers a significant economic toll on the United States healthcare system. This study aims to characterize current trends and features of the cholecystectomy population and identify factors that influence the length of stay and total charges. Methods: Case information was extracted for laparoscopic and open cholecystectomies from 2013-2016 using the New York Statewide Planning and Research Cooperative System (SPARCS) database. Descriptive, comparative, and multivariable linear regression analysis was conducted on 58,141 cases assessing age group, race, gender, admission presentation, surgical technique, insurance status, year of operation and severity of illness by the length of stay and total charges. Results: Of all procedures, 91.6% were laparoscopic, and 79.4% were emergent on admission. Total procedures trended down, while laparoscopic and emergent cases steadily increased (p<0.0001). Total charges increased during the study period, while the length of stay decreased (p<0.0001). Open and emergent procedures were associated with a higher cost and longer inpatient stays (p<0.0001). Open procedures were proportionally more common among elderly, male patients, and in elective cases (p<0.0001). Emergent presentation was more common in females, non-whites, and younger patients (p<0.0001). Regression model showed that male gender, open operation, Black race, and emergent presentation were independent predictors for a longer stay and greater total charges (p<0.0001). Medicare insurance predicted lower total charges but longer length of stay (p<0.0001). Conclusion: Race, insurance, procedure type, and patient presentation influence hospital charges and stays following cholecystectomy. Understanding these trends will allow policymakers and providers to limit the healthcare burden of cholecystectomy.

Guiwen Ye, Peng Wang, Zhongyu Xie et al.

Abstract Background Mesenchymal stem cells (MSCs) are the major source of osteoblasts. Long noncoding RNAs (lncRNAs) are abundantly expressed RNAs that lack protein‐coding potential and play an extensive regulatory role in cellular biological activities. However, the regulatory network of lncRNAs in MSC osteogenesis needs further investigation. Methods QRT‐PCR, western blot, immunofluorescence, and immunohistochemistry assays were used to determine the levels of relevant genes. The osteogenic differentiation capability was evaluated by using Alizarin Red S (ARS) staining, alkaline phosphatase activity assays, hematoxylin & eosin staining or micro‐CT. RNA fluorescence in situ hybridization (FISH) and RNAscope were used to detect HHAS1 expression in cells and bone tissue. A microarray assay was performed to identify differentially expressed microRNAs. RNA immunoprecipitation and RNA pull‐down were used to explore the interactions between related proteins and nucleic acids. Results The level of lncRNA HHAS1 increased during bone marrow‐derived MSC (BMSC) osteogenesis and was positively related to the levels of osteogenic genes and ARS intensity. HHAS1 was located in both the cytoplasm and the nucleus and was expressed in human bone tissue. HHAS1 facilitated BMSC osteogenic differentiation by downregulating miR‐204‐5p expression and enhancing the level of RUNX family transcription factor 2 (RUNX2). In addition, interferon regulatory factor 2 (IRF2) was increased during BMSC osteogenic differentiation and interacted with the promoter of HHAS1, which resulted in the transcriptional activation of HHAS1. Furthermore, IRF2 and HHAS1 helped improve bone defect repair in vivo. Conclusions Our study identified a novel lncRNA, HHAS1, that facilitates BMSC osteogenic differentiation and proposed a role for the IRF2/HHAS1/miR‐204‐5p/RUNX2 axis in BMSC osteogenesis regulation. These findings help elucidate the regulatory network of BMSC osteogenesis and provide potential targets for clinical application.

Simona De Summa, Katia Danza, Brunella Pilato et al.

Colorectal cancer (CRC) is one of the most common cancer types around the world. The prognosis of patients with advanced diseases is still poor in spite of currently available therapeutic options. Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved to treat refractory metastatic colorectal cancer (mCRC). We investigated Somatic mutations in several genes involved in immunological response and cancer progression in both long/short responder mCRC patients who underwent third-line therapy with regorafenib to identify predictive biomarkers of response using Ion Torrent PGM sequencing and bioinformatic tools. We found Somatic mutations in TGFBR1, TGFBR2, and TGFBR3 genes in primary tumor and metastases samples of long-responder patients. Furthermore, our bioinformatic results show that they were mainly enriched in immune response, cell junction, and cell adhesion in long responder patients, particularly in primary tumor and metastatic sites. These data suggest that the TGF-b pattern could be the leading actor of a prolonged response to this drug.

Anitha P Govind, Okunola Jeyifous, Theron A Russell et al.

Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear. Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation. In exploring the basis of these N-glycosylation alterations, we discovered that they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite. Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130. They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway. These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors. Neural activity thus boosts the activity of the dendrite’s satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites. This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.

Sergiu Bogdan POP, Nicolae POP, Marius MILUȚ et al.

The paper aims to conduct a research, in order to analyze how to systematically register properties in the integrated system of cadastre and land book of buildings on the territory of three cadastral sectors belonging to the administrative-territorial unit Mediaș, Sibiu County. The objective of the work is represented by the accomplishment of the systematic cadastral works in the analyzed area. The instrument used to carry out the geodetic and topographic works necessary to carry out this project is the Leica TC (R) 407 total station, which is part of the TPS400 range. The verification of the support network was performed both from a planimetric point of view using the conditional measurements method and altimetrically using the trigonometrical leveling at long distance method. Two new points were included, the compensation of their coordinates was made using the indirect measurements method. In the present paper, the real estate fund cadastre was made, the evidence and the systematic inventory were made, from a quantitative, qualitative and legal point of view of the 56 buildings from the 3 cadastral sectors afferent to the studied administrative-territorial unit. Following the work, it is found that the method of registration in the Land Book through the Systematic Cadastre is an efficient solution and an alternative to the Sporadic Cadastre addressed at national level that facilitates field work, time and allows the determination of land areas in cadastral sectors. with better accuracy.