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Introduction: Renal failure, encompassing both acute and chronic forms, stands as a formidable public health challenge with far-reaching consequences for individual well-being and healthcare systems. This study delves into the mortality rates of renal failure in the United States over two transformative decades, from 1999 to 2020. Renal failure’s significance arises from its escalating prevalence, substantial healthcare costs, and the imperative to understand the multifaceted factors that influence its outcomes. Objectives: The primary objectives of this research are to analyze temporal trends in renal failure mortality rates, explore the impact of the Affordable Care Act (ACA) and advancements in renal care practices on mortality rates, and assess demographic disparities in mortality outcomes. Methods: Utilizing CDC WONDER’s multi-cause mortality data, we assessed mortality due to renal failure (ICD-10 Codes: N17–N19). Age-adjusted mortality rates (AAMRs) were collected and stratified by sex and race. The Joinpoint Regression Program analyzed trends, calculating annual percent change (APC) and significant average annual percent change (AAPC) from 1999 to 2020. Segmented line regression models were employed for parallel pairwise comparisons. Results: Renal failure mortality rates decreased for both sexes during the late 2000s. The ACA’s enactment in 2010 coincided with improved access to healthcare, possibly contributing to the decline. Demographic disparities highlighted variations in mortality rates across racial and gender groups. Advancements in renal care practices were evident, which were driven by innovations in treatment modalities and disease management. Significant temporal trends were observed by race, with varying periods of decrease or uptrend. Conclusions: The decline in renal failure mortality rates during the late 2000s was potentially influenced by the ACA and advances in renal care practices. Demographic disparities emphasize the need for equitable healthcare access and interventions. These findings underscore the significance of healthcare policies and medical advancements in reducing renal failure mortality rates and addressing disparities. Persistent efforts to mitigate challenges such as healthcare access, cost barriers, and disparities remain crucial to enhancing renal failure outcomes.

Mohamed A Hendaus,1,2 Hibaq A Jama,1 Faisal J Siddiqui,1,3 Sohair A Elsiddig,1 Ahmed H Alhammadi1,2 1Department of Pediatrics, General Academic Pediatrics Section, Hamad Medical Corporation, Doha, 2Department of Clinical Pediatrics, Weill Cornell Medical College, 3Pediatric Residency Program, Hamad Medical Corporation, Doha, Qatar Objective: The objective of this study was to investigate parental preference for fluoride varnish in a country where the average percentage of dental caries in young children is up to ~73%. Consequently, the aim of this study, despite being a pilot, was to create a nationwide project in the State of Qatar to promote oral health in children. Methods: A cross-sectional perspective study was conducted at Hamad Medical Corporation in Qatar. Parents of children aged ≤5 years were offered an interview survey. A total of 200 questionnaires were completed (response rate =100%). The study was conducted between December 1, 2014 and March 30, 2015, and included all children aged >1 year and 90% of families were aware that dental health affects the health of the whole body. The study showed that ~70% of parents were not aware of the existence of fluoride varnish, but would allow a health provider to apply fluoride varnish. Furthermore, ~80% of parents would not stop brushing their child’s teeth and would not skip dentist appointments if varnish was to be applied. Approximately 40% of parents conveyed some concerns regarding the safety of fluoride varnish, despite being considered as a new concept. The main concern was that the child might swallow some of the fluoride. Another important concern expressed by parents was the availability of the fluoride varnish in all clinics. Conclusion: The robust positive attitude of parents in this sample suggests that introducing fluoride varnish is feasible and acceptable in our community. Actions to augment fluoride varnish acceptability in the developing world, such as focusing on safety, could be important in the disseminated implementation of fluoride varnish. Keywords: fluoride, parents, varnish, Qatar

Aims: Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations., Methods and Results: We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%)., Conclusion: Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Primary care physicians (PCPs) are doctors in primary health care institutions, namely village clinics, township health centers and community health service centers (stations) who are the main providers of primary health care services in primary health care settings. Improving the overall health status of the population requires the support of a large number of primary care physicians; however, the job satisfaction of this group has not been sufficiently emphasized and recognized., Objective: The purpose of this study was to examine the effects of primary care physicians' work-family conflict on their job satisfaction, as well as the mediating role of burnout and the moderating role of social support., Methods: This cross-sectional study was conducted from February 2023 to March 2023. Participants were 749 primary care physicians from four cities of Xuzhou, Linyi, Huaibei, and Shangqiu in the Huaihai Economic Zone of China. SPSS statistical analysis was used to evaluate the relationship between work-family conflict, social support, burnout and job satisfaction among medical workers., Results: Work-family conflict had a significant negative effect on job satisfaction ( β = -0.36, p < 0.001), after adding burnout in the model, work-family conflict also negatively predicted job satisfaction ( β = -0.32, p < 0.001). Social support had a moderating effect on the direct effect of burnout on job satisfaction ( β = 0.00, t = 2.66, p < 0.01, 95% CI [0.001, 0.007]), the predictive effect of burnout on job satisfaction at high level of social support ( β = -0.45, p < 0.001) was higher than a low level of social support ( β = -0.33, p < 0.001)., Conclusions: This study demonstrated the negative impact of work-family conflict on primary care physicians' job satisfaction, as well as the mediating role of burnout and the moderating role of social support on burnout and job satisfaction, which are important for improving primary care physicians' job satisfaction and enhancing the quality of primary care in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wen, Wu, Bai, Jintao, Zhao, Fang and Abdirizak Jama.)

In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency of KIT , PDGFRA , and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15-91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation: KIT (61%), PDGFRA (25%), NF1 (2%), and one NTRK1 rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5-8.0) ( p = 0.018), with mitosis ≤5/5 mm 2 , and were of lower risk ( p = 0.019). KIT mutations were an adverse indicator of disease progression ( p = 0.049), while wild-type status did not significantly impact progression ( p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants.

Aims: Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait., Methods: We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations., Results: Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2-17.6) and 21 adult patients (median 37 years; 18.9-89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs., Conclusion: The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This article provides an in-depth review of the current state of management for diabetes, hypertension, and cardiovascular disease, focusing on advancements from genomics to robotics. It explores the role of genomic markers in personalized medicine, offering tailored treatment options for these chronic conditions. The article also examines the efficacy of various pharmacological and surgical interventions, including bariatric surgery for diabetes and device-based treatments for hypertension. A comparative analysis is presented to evaluate the cost-effectiveness and patient outcomes between medical and surgical approaches. The review concludes that while personalized medicine and minimally invasive surgical techniques show promise, more high-quality comparative research is needed. The ultimate goal is to integrate these emerging technologies within a framework of evidence-based medicine to improve patient outcomes and health equity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Tanveer et al.)

Importance: The new diagnostic code for pediatric feeding disorder (PFD) in the International Classification of Diseases, 10th edition, Clinical Modification, requires that occupational therapists and speech-language pathologists (SLPs) use valid and reliable assessment tools that capture the complexity of PFD., Objective: To determine current assessment tools that clinicians are using across the four domains of PFD: (1) medical factors, (2) nutrition factors, (3) feeding skill factors, and (4) psychosocial factors. A secondary objective was to obtain clinicians' perceptions of the assessment tools., Design: A mixed-methods study using survey research and focus groups., Setting: Online survey and virtual focus groups., Participants: Occupational therapists and SLPs who identified as clinicians who treat PFDs., Results: The survey revealed that 65% of the clinicians (N = 445) used a nonstandardized assessment tool across the four domains of PFD. The focus groups (n = 26) revealed four resulting themes that expanded the survey results: (1) no one assessment tool works, (2) clinicians rely on self-created assessments, (3) it takes a team and collaboration, and (4) there are many issues with the current assessment of PFD., Conclusions and Relevance: This study reveals the need for clinicians working with children with PFD to use feeding assessment tools with sound psychometric properties. The requirement for occupational therapists and SLPs to evaluate and treat dysphagia and disorders of feeding indicates the need to provide entry-level education on reliable and valid assessment tools that thoroughly evaluate all the domains of PFD. What This Article Adds: This article highlights current assessment tools used by occupational therapists and SLPs treating PFD and the need for more standardized procedures and tools to evaluate children across the four domains of PFD., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)

Glaucoma is the largest cause of irreversible blindness with a multifactorial genetic etiology. This study explores novel genes and gene networks in familial forms of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) to identify rare mutations with high penetrance. Thirty-one samples from nine MYOC -negative families (five POAG and four PACG) underwent whole-exome sequencing and analysis. A set of prioritized genes and variations were screened in an independent validation cohort of 1536 samples and the whole-exome data from 20 sporadic patients. The expression profiles of the candidate genes were analyzed in 17 publicly available expression datasets from ocular tissues and single cells. Rare, deleterious SNVs in AQP5, SRFBP1, CDH6 and FOXM1 from POAG families and in ACACB, RGL3 and LAMA2 from PACG families were found exclusively in glaucoma cases. AQP5, SRFBP1 and CDH6 also revealed significant altered expression in glaucoma in expression datasets. Single-cell expression analysis revealed enrichment of identified candidate genes in retinal ganglion cells and corneal epithelial cells in POAG; whereas for PACG families, retinal ganglion cells and Schwalbe's Line showed enriched expression. Through an unbiased exome-wide search followed by validation, we identified novel candidate genes for familial cases of POAG and PACG. The SRFBP1 gene found in a POAG family is located within the GLC1M locus on Chr5q. Pathway analysis of candidate genes revealed enrichment of extracellular matrix organization in both POAG and PACG.

Aims: Accurate assessment of 1p/19q codeletion status in diffuse gliomas is of paramount importance for diagnostic, prognostic and predictive purposes. While targeted next generation sequencing (NGS) has been widely implemented for glioma molecular profiling, its role in detecting structural chromosomal variants is less well established, requiring supplementary informatic tools for robust detection. Herein, we evaluated a commercially available amplicon-based targeted NGS panel (Oncomine Comprehensive Assay v3) for the detection of 1p/19q losses in glioma tissues using an Ion Torrent platform and the standard built-in NGS data analysis pipeline solely., Methods: Using as little as 20 ng of DNA from formalin-fixed paraffin-embedded tissues, we analysed 25 previously characterised gliomas for multi-locus copy number losses (CNLs) on 1p and 19q, including 11 oligodendrogliomas (ODG) and 14 non-oligodendroglial (non-ODG) controls. Fluorescence in-situ hybridisation (FISH) was used as a reference standard., Results: The software confidently detected combined contiguous 1p/19q CNLs in 11/11 ODGs (100% sensitivity), using a copy number cut-off of ≤1.5 and a minimum of 10 amplicons covering the regions. Only partial non-specific losses were identified in non-ODGs (100% specificity). Copy number averages of ODG and non-ODG groups were significantly different (p<0.001). NGS was concordant with FISH and was superior to it in distinguishing partial from contiguous losses indicative of whole-arm chromosomal deletion., Conclusions: This commercial NGS panel, along with the standard Ion Torrent algorithm, accurately detected 1p/19q losses in ODG samples, obviating the need for specialised custom-made informatic analyses. This can easily be incorporated into routine glioma workflow as an alternative to FISH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

In a large family of Czech origin, we mapped a locus for an autosomal-dominant corneal endothelial dystrophy, posterior polymorphous corneal dystrophy 4 (PPCD4), to 8q22.3-q24.12. Whole-genome sequencing identified a unique variant (c.20+544G>T) in this locus, within an intronic regulatory region of GRHL2. Targeted sequencing identified the same variant in three additional previously unsolved PPCD-affected families, including a de novo occurrence that suggests this is a recurrent mutation. Two further unique variants were identified in intron 1 of GRHL2 (c.20+257delT and c.20+133delA) in unrelated PPCD-affected families. GRHL2 is a transcription factor that suppresses epithelial-to-mesenchymal transition (EMT) and is a direct transcriptional repressor of ZEB1. ZEB1 mutations leading to haploinsufficiency cause PPCD3. We previously identified promoter mutations in OVOL2, a gene not normally expressed in the corneal endothelium, as the cause of PPCD1. OVOL2 drives mesenchymal-to-epithelial transition (MET) by directly inhibiting EMT-inducing transcription factors, such as ZEB1. Here, we demonstrate that the GRHL2 regulatory variants identified in PPCD4-affected individuals induce increased transcriptional activity in vitro. Furthermore, although GRHL2 is not expressed in corneal endothelial cells in control tissue, we detected GRHL2 in the corneal "endothelium" in PPCD4 tissue. These cells were also positive for epithelial markers E-Cadherin and Cytokeratin 7, indicating they have transitioned to an epithelial-like cell type. We suggest that mutations inducing MET within the corneal endothelium are a convergent pathogenic mechanism leading to dysfunction of the endothelial barrier and disease., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Allergies are a growing health concern with a significant impact on quality of life and healthcare costs. It is critical to develop an appropriate care plan to deal with children's allergies. This study aimed to assess and compare the knowledge and perception of families and school personnel caring for children with history of anaphylaxis who were prescribed the epinephrine autoinjector (EpiPen). The study also examined the underlying reasons for any observed knowledge gaps., Methods: A cross-sectional study of 128 families and 50 corresponding school personnel caring for children at risk of anaphylaxis who had been prescribed the EpiPen was conducted. The primary outcome was to identify any knowledge deficiency within family and school personnel and the reasons behind knowledge gaps., Results: Of the 128 screened schools, 30 (23%) were not informed by parents about their pupils' risk of anaphylaxis. Importantly, 113 (88%) of families and 42 (84%) of schools were unable to recognise the symptoms of anaphylaxis. Also, 67 (52%) of families and 22 (44%) of schools were not aware that a child should ideally have two EpiPen in case of a severe allergic reaction. The EpiPen had been used by 18 (14%) families and 5 (6%) schools., Discussion: Communication among families and school personnel regarding anaphylaxis was suboptimal. Both parents and school personnel lacked key information in allergy management. Managing a child at risk of anaphylaxis requires effective communication among healthcare professionals, families and schools. There is an urgent need to improve knowledge of anaphylaxis and its management among families and school caregivers., Competing Interests: Competing interests: None declared.

Purpose: To characterize the histological appearance and expression of pro-inflammatory mediators, growth factors, matrix metalloproteinases and biomarkers of epithelial-mesenchymal transition (EMT) in healthy control and trachomatous trichiasis (TT) conjunctival tissue., Methods: Conjunctival biopsies were taken from 20 individuals with TT and from 16 individuals with healthy conjunctiva, which served as controls. Study participants were of varying ethnicity and were living in a trachoma-endemic region of northern Tanzania. Formalin-fixed paraffin-embedded tissue sections were stained using hematoxylin and eosin or by immunohistochemistry using antibodies against: IL-1β, IL-6, IL-17A, IL-22, CXCL5, S100A7, cleaved caspase 1 (CC1), PDGF, CTGF, TGFβ2, MMP7, MMP9, E-cadherin, vimentin, and αSMA., Results: Tissue from TT cases had a greater inflammatory cell infiltrate relative to controls and greater disruption of collagen structure. CTGF and S100A7 were more highly expressed in the epithelium and IL-1β was more highly expressed in the substantia propria of TT cases relative to controls. Latent TGFβ2 was slightly more abundant in the substantia propria of control tissue. No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of EMT biomarkers., Conclusions: These data indicate that the innate immune system is active in the immunopathology of trachoma, even in the absence of clinical inflammation. CTGF might provide a direct link between inflammation and fibrosis and could be a suitable target for therapeutic treatment to halt the progression of trachomatous scarring.

In order to provide baseline data for an immuno-parasitological laboratory in Somalia, serum concentrations of IgG, IgM and IgA were determined in some key populations: healthy residents of Mogadishu (n = 157), inhabitants of the village of Daimo Samo (n = 276) and patients with malaria (n = 39) and visceral leishmaniasis (n = 26), both protozoan infections accompanied by hypergammaglobulinaemia and causing severe health problems in Somalia. Since the serum immunoglobulin concentrations in the Somali populations studied were not normally distributed, they were evaluated using medians and percentiles. Significantly higher values of IgG, IgM and IgA were demonstrated in healthy Mogadishu residents as compared to healthy Swedes. Daimo Samo villagers had significantly higher IgG and IgM values than healthy Mogadishu residents. Very high concentrations of IgG and IgM were demonstrated in sera from patients with visceral leishmaniasis. Somali patients with malaria also had marked hypergammaglobulinaemia, however, only in the IgG class. The high levels of IgG, IgM and IgA demonstrated in sera from Somalis, indicate the need for establishing local reference values and should be considered when introducing serological tests in tropical countries. Such methods are usually adopted to conditions in industrialized countries, where immunoglobulin contents of sera are lower.