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  • CrossCountry passengers face strike disruption on bank holiday weekend | Rail industry

    CrossCountry passengers face strike disruption on bank holiday weekend | Rail industry

    Rail passengers have been warned that a strike by rail workers could disrupt services on the bank holiday weekend when transport networks are expected to be packed with holidaymakers.

    Members of the Rail, Maritime and Transport (RMT) union at the operator CrossCountry are going on strike on Saturday 23 August and bank holiday Monday over pay and conditions.

    The company, whose network is centred around Birmingham and runs to cities across Great Britain from Aberdeen in the north to Cornwall in the south, said it would offer a reduced timetable over the weekend with no services on Saturday and cancellations expected across all routes on Sunday.

    Visit England has reported that more than 11 million Britons are planning an overnight trip in the UK over the bank holiday break in England and Wales, which would mark an increase on the same weekend a year earlier.

    CrossCountry is advising passengers not to travel on Saturday but to travel instead on either side of the weekend, or to claim a full refund.

    The train operator said a “very limited” service would operate on Monday between 8am and 6pm, and advised passengers to check their journeys before departing.

    Further journey details will be available on CrossCountry’s website in the coming days but it said there would be no service between Birmingham, Reading and the south coast, and no service between Leicester, Cambridge and Stansted airport. Only very limited services will run to south-west England and north of York.

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    Planned engineering work in the West Midlands is also expected to have an impact on the CrossCountry services that are running, meaning some journeys will take longer.

    Shiona Rolfe, the managing director of CrossCountry, which is owned by Arriva UK Trains, said: “It is hugely disappointing to not operate any services on Saturday, knowing the inevitable disruption to many of our passengers’ journeys over the bank holiday weekend. We are committed to reaching an agreement with the RMT and remain available to continue talks.”

    An RMT spokesperson said: “Our members have voted strongly in favour of industrial action and we are seeking further talks with management to bring about a negotiated settlement.”

    In June, RMT members at CrossCountry began an overtime ban and also started to refuse to work on rest days, as they accused the company of declining to negotiate over increased pay for overtime and rest-day working, which it said went against previously agreed commitments.

    The coach operator National Express said it was increasing capacity on its intercity services over the bank holiday weekend in response to strike action, adding 9,000 extra seats on routes including Birmingham, Cardiff, London, Leeds, Manchester and Nottingham.

    Motorists have been warned they could face long delays on the roads over the weekend, when 18m car journeys are expected to take place, while the RAC has advised travellers to set off as early as possible.

    The heaviest congestion is expected in the south-east and south-west of England, while delays are expected on the M20 in Kent for drivers crossing the Channel from Dover or Folkestone.

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  • Global shares are mixed, while Labubu maker Pop Mart soars 12.5% in Hong Kong

    Global shares are mixed, while Labubu maker Pop Mart soars 12.5% in Hong Kong

    TOKYO — Global shares were mostly lower on Wednesday, tracking a decline on Wall Street led by technology shares including Nvidia and other artificial-intelligence stars.

    France’s CAC 40 slipped 0.1% to 7,967.89, while in Germany the DAX dipped 0.4% to 24,333.63. Britain’s FTSE 100 lost 0.1% to 9,177.91.

    Futures for the S&P 500 and the Dow Jones Industrial Average were 0.2% lower.

    In Asia, benchmarks fell in Japan, South Korea and Taiwan, weighed down by selling of shares in computer chip-related companies.

    Tokyo’s benchmark Nikkei 225 declined 1.5% to close at 42,888.55.

    Japan reported its exports fell slightly more than expected in July, down 2.6% from the same month a year ago, pressured by higher tariffs on goods shipped to the U.S. Imports also fell, dropping 7.5% from a year ago. Exports to the U.S. fell 10.1%, while imports slipped 0.8%.

    Computer-chip equipment makers Advantest plunged 5.7% and Disco Corp. dropped 4.9%. Chip maker Tokyo Electron lost 1.4%. and Lasertec Corp. lost 1.7%.

    The Taiex in Taiwan fell 3.0% after chip maker TSMC dropped 4.2%.

    Hong Kong’s Hang Seng gained nearly 0.2% to 25,165.94, while the Shanghai Composite index gained 1.0% to 3,766.21 after China’s central bank opted to keep the benchmark interest rate unchanged, as markets had expected.

    Chinese toy company Pop Mart International Group’s shares traded in Hong Kong soared 12.5% after its CEO said its annual revenue could top $4 billion this year, more than quadrupling after more than doubling in the first half of the year. Its CEO also announced that the company was releasing a mini version of its popular Labubu dolls.

    Australia’s S&P/ASX 200 gained nearly 0.3% to 8,918.00.

    South Korea’s Kospi dropped 0.7% to 3,130.09, after North Korean leader Kim Jong Un condemned South Korean-U.S. military drills that began this week. He vowed a rapid expansion of his nuclear forces to counter rivals, according to North Korean state media.

    The week’s headliner for Wall Street is likely arriving on Friday. That’s when the chair of the Federal Reserve, Jerome Powell, will give a highly anticipated speech in Jackson Hole, Wyoming. The setting has been home to big policy announcements from the Fed in the past, and the hope on Wall Street is that Powell may hint that cuts to interest rates are coming soon.

    The Fed has kept its main interest rate steady this year, primarily because of the fear of the possibility that President Donald Trump’s tariffs could push inflation higher. But a surprisingly weak report on job growth across the country may be superseding that.

    On Tuesday the S&P 500 fell 0.6% and the Dow gained less than 0.1%. The Nasdaq composite slumped 1.5%.

    The heaviest weight on the market was Nvidia, whose chips are powering much of the move into AI. It sank 3.5%.

    Another AI darling, Palantir Technologies, dropped 9.4% for the largest loss in the S&P 500. It’s seen bets build up sharply that its stock price will drop, according to S3 Partners. Only Meta Platforms has seen a bigger increase this year in what’s called “short interest,” where traders essentially bet a stock’s price will fall. Meta, the owner of Facebook and Instagram, sank 2.1%.

    In other dealings early Wednesday, benchmark U.S. crude added 65 cents to $63.00 a barrel. Brent crude, the international standard, gained 68 cents to $66.47 a barrel.

    The U.S. dollar edged down to 147.54 Japanese yen from 147.66 yen. The euro fell to $1.1640 from $1.1648.

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  • Sharp rise in airfare and food costs pushed UK inflation higher in July, denting rate cut hopes

    Sharp rise in airfare and food costs pushed UK inflation higher in July, denting rate cut hopes

    LONDON — Higher food and airfare prices pushed U.K. inflation above expectations in July, official figures showed Wednesday, which has tempered market expectations that the Bank of England will cut interest rates again this year.

    The Office for National Statistics said consumer price inflation was 3.8% in the year to July, up from 3.6% in June. One of the contributors was airfares soaring by 30.2% between June and July, the biggest jump since the collection of monthly data began in 2001.

    Most economists had anticipated a more modest rise in inflation to 3.7%.

    With inflation now at its highest rate since January 2024 and nearly double the Bank of England’s target of 2%, the prospects of another rate cut in 2025 are diminishing.

    “July’s outturn probably extinguishes hope of a September interest rate cut, while strengthening underlying inflationary pressures calls into question whether policymakers will be able to relax policy again this year,” said Suren Thiru, economics director at the chartered accountants institute ICAEW.

    The bank cut its main interest rate by a quarter of a percentage point to 4% earlier this month, its fifth reduction in a year, when policy makers began lowering borrowing costs from a 16-year high of 5.25%.

    The Bank of England’s key rate, a benchmark for mortgages as well as consumer and business loans, is now at the lowest level since March 2023.

    The latest increase is another blow to the Labour government, which was partly propelled into power last July because of the cost-of-living crisis, which saw inflation rise to over 11% at one time.

    Treasury chief Rachel Reeves acknowledged there was “more to do to ease” the cost-of-living.

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  • Google Docs Now Reads Your Work Aloud with Gemini AI

    Google Docs Now Reads Your Work Aloud with Gemini AI

    Google has introduced a new Gemini-powered “Audio” feature in Docs that allows documents to be read aloud in natural, human-like voices. Far from the monotone text-to-speech tools of the past, this update makes written content sound more like a collaborator than a machine. It is:

    • Accessibility win: Provides inclusive support for users who depend on audio.
    • Productivity boost: Lets users review content while multitasking.
    • Editing advantage: Hearing text read aloud helps catch errors that are easy to miss visually.

    How Gemini AI Voiceover Works

    Using the feature is simple. On desktop, open your document and head to:

    Tools > Audio > Listen to this tab.

    An elegant floating audio player appears, giving users full control over playback. You can play, pause, scrub through the text, adjust reading speed, and even switch between different voices. Authors can embed a customizable Audio button inside the document itself, letting collaborators press play directly within the file.

    Beyond Read-Aloud: Voice With Personality

    Google has added voice styles like Educator, Motivator, and Coach, each designed to bring a distinct tone. A research paper can now sound like a lecture, while a training manual can feel like a guided session.

    This makes Docs more versatile: equally useful for professional editing, personal productivity, and creative storytelling.

    Gemini AI Accessibility at Its Core

    Users with visual impairments or reading challenges can now access a live narrator directly inside Google Docs. At launch, the feature is available in English only, and limited to Workspace Business, Enterprise, and Education plans, along with AI Pro and Ultra subscribers.

    The update aligns with Google’s broader push into audio-first experiences. From Gemini-powered Audio Overviews to NotebookLM’s podcast-style summaries, the company is steadily transforming Docs into more than just a writing tool—it’s becoming a creative and collaborative workspace.

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  • Heavy rain lashes northern Japan, triggers evacuations and disrupts transport, say local media

    Heavy rain lashes northern Japan, triggers evacuations and disrupts transport, say local media




    (Reuters) – Torrential rain lashed northern Japan on Wednesday, prompting evacuation orders and advisories across multiple cities, according to local media reports.

    In Akita Prefecture, cars were seen navigating streets amid heavy rain the city of Odate. An emergency evacuation advisory was issued for Semboku City, where a river had flooded. The city recorded 244.5 millimetres (9.6 inches) of rainfall in the 24 hours leading up to 2 pm (0500 GMT), public broadcaster NHK reported.

    Heavy rain disrupted water supply to around 70 households in Semboku, while at least 28 people were stranded, NHK said.

    Evacuation orders were also issued for parts of Kazuno and Kitaakita cities, according to Japanese broadcaster Nippon TV. Train services were suspended in Akita and neighbouring Aomori Prefecture, which saw record rainfall. 


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  • Scientists debut a new foundational atlas of the plant life cycle

    Scientists debut a new foundational atlas of the plant life cycle

    Scientists debut a new foundational atlas of the plant life cycle

    Salk Institute researchers map every cell type and developmental state across the entire life cycle of model plant Arabidopsis

    LA JOLLA—Nearly everything you know about plants was first discovered in a plant you’ve likely never heard of. Arabidopsis thaliana, also known as thale cress, is a small, flowering weed that has shaped much of plant biology as we know it. Serving as the representative plant species in most plant research across the last half century, Arabidopsis has taught us how plants respond to light, which hormones control plant behavior, and why some plants grow long, deep roots while others grow them shallow and wide. But despite its beloved reputation among plant biologists worldwide, many elements of the Arabidopsis life cycle have remained a mystery.

    Arabidopsis thaliana spatial transcriptomic assay shows the striking cellular diversity in the plant’s flower, as each color represents a distinct cell type.
    Click here for a high-resolution image.
    Credit: Salk Institute

    Salk Institute researchers have now established the first genetic atlas to span the entire Arabidopsis life cycle. The new atlas—created using detailed single-cell and spatial transcriptomics—captures the gene expression patterns of 400,000 cells within multiple developmental stages as Arabidopsis grows from a single seed to a mature plant. The publicly available resource will be hugely informative to future studies of different plant cell types and developmental stages, and how they respond to stress and environmental stimuli.

    The findings, published in Nature Plants on August 19, 2025, will help expand research and development in plant biotechnology, agriculture, and environmental sciences.

    “We’ve come very far in our understanding of plant biology, but until recently, there has been a technological bottleneck preventing us from comprehensively cataloguing cell types and the genes they express uniformly, across developmental stages,” says senior author Joseph Ecker, professor, Salk International Council Chair in Genetics, and Howard Hughes Medical Institute investigator. “Our study changes that. We created a foundational gene expression dataset of most cell types, tissues, and organs, across the spectrum of the Arabidopsis life cycle.”

    How to map a plant

    In its many years as a model plant, Arabidopsis has seen its fair share of experiments. Scientists have been working to decode Arabidopsis’ genome for decades, mapping which genes are expressed in each cell type across various plant tissues and organs. Using these incremental maps, scientists can start to figure out which genes control the identity and behavior of different parts of the plant.

    One effective way to make these maps is by using single-cell RNA sequencing. This genetic sequencing technique looks at the genome’s products—strands of RNA—rather than the original DNA code. This makes it easy for scientists to see which genes are actually used in a cell, and how many. Gene expression maps also help researchers characterize the different types of cells within a species. Since every cell in an organism contains the same genetic code, different cell types can be identified by the unique pattern of genes they express.

    Illustration capturing the study’s findings, with Arabidopsis thaliana sprouting amongst cells and strands of DNA—all inside a globe.
    Illustration capturing the study’s findings, with Arabidopsis thaliana sprouting amongst cells and strands of DNA—all inside a globe.
    Click here for a high-resolution image.
    Credit: Aga Weickoeska

    While single-cell RNA sequencing has allowed scientists to make detailed maps of cell types, these maps are often restricted to select organs or tissues—for example, looking only at the plant’s roots and ignoring the stem, flowers, and leaves. To move from small genetic maps to a sophisticated atlas, the Salk researchers paired single-cell RNA sequencing with another technology: spatial transcriptomics.

    Better technology, better maps

    With single-cell RNA sequencing, researchers are forced to separate tissues of interest and process their cells in isolation. With spatial transcriptomics, researchers can create genomic maps of plants as they exist in the real world, within the tissue context. The structure, shape, and location of cells and tissues across the entire plant can remain intact throughout the sequencing process. The result is an insightful view into the identity of cells within multiple tissues and organs at once.

    “What excites me most about this work is that we can now see things we simply couldn’t see before,” says co-first author Natanella Illouz-Eliaz, a postdoctoral researcher in Ecker’s lab. “Imagine being able to watch where up to a thousand genes are active all at once, in the real tissue and cell context of the plant. It’s not only fascinating on its own, but it’s already led us to discoveries, like finding genes involved in seedpod development that no one knew about before. There’s so much more waiting to be uncovered in this data, and that sense of possibility is what I am truly enthusiastic about.”

    The single-cell and spatial transcriptomic atlas spans 10 Arabidopsis developmental stages, from seed in the ground to flowering adulthood. More than 400,000 cells were captured across this life cycle, demonstrating the striking diversity of cell types that can be found in just one organism.

    Where the new map leads us

    By looking at the full life cycle of Arabidopsis rather than at a single snapshot in time, the researchers have already found a surprisingly dynamic and complex cast of characters responsible for regulating plant development. They also learned about many new genes whose expression and function in unique cell types can now be further explored.

    From left: Tatsuya Nobori, Natanella Illouz Eliaz, and Travis Lee.
    From left: Tatsuya Nobori, Natanella Illouz Eliaz, and Travis Lee.
    Click here for the original image.
    Credit: Salk Institute

    “This study will be a powerful tool for hypothesis generation across the entire plant biology field,” says co-first author Travis Lee, a postdoctoral researcher in Ecker’s lab. “Our easy-to-use web application makes this life cycle atlas easily accessible to the plant science community through simply navigating to our website, and we can’t wait to learn from the many single-cell genomic studies it will now enable.”

    The researchers hope this new resource—currently available for free online—will enable deeper exploration of plant cell development, help explain how plants respond to genetic and environmental perturbations, and advance the field of plant biology overall.

    Other authors include Jiaying Xu, Bruce Jow, and Joseph Nery of Salk, as well as Tatsuya Nobori, formerly of Salk and presently at The Sainsbury Laboratory in the United Kingdom.

    The work was supported by the Human Frontiers Science Program (no. LT000661/2020-L), George E. Hewitt Foundation for Medical Research, Weizmann Institute of Science, National Institutes of Health (NIGMS K99GM154136), and Howard Hughes Medical Institute.

    DOI: 10.1038/s41477-025-02072-z


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  • JPMorgan upgrades this online lender thanks to ‘favorable’ macroenvironment

    JPMorgan upgrades this online lender thanks to ‘favorable’ macroenvironment

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  • Insomnia disorders among chronic renal patients on haemodialysis: Prev

    Insomnia disorders among chronic renal patients on haemodialysis: Prev

    Introduction

    In daily clinical practice, we observed that patients with end-stage kidney disease undergoing hemodialysis often complained of symptoms of sleep disturbance, with insomnia being the most common. Insomnia, defined per Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM 5) as difficulty initiating or maintaining sleep or experiencing non-restorative sleep with daytime impairment occurring at least 3 nights per week for three months or longer.1 Studies around the world showed that the rate of sleep disorders including insomnia was very common in patients with end-stage kidney disease and on hemodialysis, with a rate ranging from 30% to 80%.2 In Vietnam, Phan The Thanh’s study showed that 66.4% of patients with end-stage chronic kidney disease undergoing hemodialysis had poor sleep quality.3 Phan The Thanh et al highlighted a high prevalence of sleep disturbances among Vietnamese hemodialysis patients, emphasizing the need for further investigation in this context. Prior studies have identified factors such as anxiety, depression, prolonged hemodialysis duration, co-morbidities, sex, age and psychosocial stressors as contributors to insomnia in hemodialysis patients.4–6 However, data from Vietnam were limited.

    Insomnia, if not well managed, leads to dysfunction of organ systems in the body, such as the cardiovascular and neuroendocrine systems, reducing the patient’s quality of life and higher mortality risk,7 and could lead to more serious psychiatric disorders such as anxiety, depression, and even suicide.8 The study by Ye et al indicated that the prevalence of depression and anxiety in hemodialysis patients was 68.93% and 36.89%, respectively,9 while the study by Nagy et al reported corresponding rates of 55% and 49.6%.10 Despite the growing evidence, few studies have comprehensively examined the prevalence and associated factors of insomnia in Vietnamese dialysis patients. While many studies rely on screening tools such as The Pittsburgh Sleep Quality Index (PSQI)3,11 or Insomnia Severity Index (ISI)12 to assess insomnia not using clinical criteria such as DSM 5. DSM 5 provides standardized criteria for diagnosing insomnia disorder base on clinical interviews, but objective measures like polysomnography are often limited by resource constraints, particularly in developing countries.1 Therefore, this study addressed this gap by investigating the prevalence of insomnia, diagnosed using DSM 5 criteria, and its associated factors in hemodialysis patients may support the development of management strategies, though further research is needed to confirm impacts on treatment outcomes and complications. This study aimed to estimate prevalence of insomnia and identify associated factors among hemodialysis patients in Vietnam.

    Subjects and Methodology

    Subjects

    A total of 216 patients over 18 years of age with end-stage kidney disease on hemodialysis were selected from their medical records at the Department of Nephrology and Hemodialysis, 175 Military Hospital, Ho Chi Minh City, from September 2023 to July 2024. Patients were invited to enroll in the study if they met the following inclusion criteria: over 18 years of age, on hemodialysis for at least three months, signed the written informed consent form, and had the ability to answer the questionnaire. Exclusion criteria were follows: Patient under 18 years old, those with severe psychiatric disorders (eg, schizophrenia, bipolar disorder, acute psychosis…), severe physical illness (eg, severe heart failure, terminal cancer…), severe cognitive impairment, individuals with hearing or visual impairments preventing completion of the questionnaire, and those who did not consent to participate in the study.

    Size of Sample

    The sample size was calculated using the formula for evaluating disorder prevalence in the community.

    n= [z2(1-a/2) * p(1-p)]/d2

    n: number of participants, Z(1-a/2) = 1.96 (confidence interval: 95%), d: 0.05, p = 83.8%.6 The sample size was calculated based on an expected insomnia prevalence from Al – Ali F’s study,6 with ± 5% precision and 95% confidence. We estimated that the sample size required for statistical significance should include at least 209 participants. Eligible participants were selected using a convenient sampling due to resource and feasibility constraints, with all eligible patients at the hospital during the study period invited to participate. During the study period, we selected 216 patients with end-stage kidney disease on hemodialysis.

    Methods

    Research Design

    This cross-sectional study included descriptive and statistical analyses.

    Data Measurement

    DSM 5 criteria was used to diagnose insomnia based on critical criteria (coded in DSM 5 as 780.52) in the participants. The diagnosis was made by two independent psychiatrists who were not included in the research group. Insomnia diagnosis was based on a standardized clinical interview following DSM 5 criteria. If the diagnosis between the two psychiatrists is different, a third psychiatrist was invited to re-diagnose and the final diagnosis was the diagnosis of the two people with the same diagnosis, ensuring high inter-rater reliability (Cohen’s Kappa, κ=0.85). These psychiatrists all have clinical experience of 10 years or more.

    To collect data on risk factors associated with insomnia, participants used a structured questionnaire on sociodemographic information such as age, sex, occupation, economic status, marital status, level of education, income per year, clinical information including duration of chronic kidney failure (defined as duration since diagnosis of chronic kidney disease (in months)), duration of hemodialysis (defined as duration of treatment since initiation (in months)), number of hemodialysis sessions per week. Clinical data were extracted from medical records including co-morbidities such as diabetes mellitus, hypertension, dyslipidemia, other kidney diseases, anemia, blood pressure, body mass index, plasma urea level, and plasma creatinine level within 24 hours prior to the hemodialysis session. Information related to health behaviors such as alcohol consumption and smoking was also collected. In addition, other factors such as napping or sleeping during the day, whether the bedroom is noisy or has a lot of light, using TV, phone too much before bedtime, and having stressful events/conflicts in the past three months were also surveyed. Questionnaire to explore the risk factors based on previous studies on insomnia in hemodialysis patients, focusing on common clinical, psychosocial factors and sleep environmental factors; pilot-tested on 20 patients for clarity and cultural and health setting appropriateness. No data were missing in this study, as all required variables were fully collected.

    Statistical Analysis

    All statistical analyses were performed using SPSS version 20.0. Chi-square tests were used to measure differences in characteristics between those with and without insomnia; for the categorical variables with expected cell counts less than 5, we used Fisher’s exact test instead of the chi-square test to ensure statistical validity. For continuous variables (eg, age, hemodialysis duration, body mass index, plasma urea…) were described using means and standard deviations or median and IQR. To compare means or median between two groups (insomnia group vs non-insomnia group) we used t test for normally distributed data, for non-normally distributed data, we applied the Mann–Whitney U-test. The Odds ratios (OR) and its 95% confidence intervals (CIs) were estimated. Statistical significance was set at p <0.05. Univariate and Multivariate logistic regression analyses were employed to identify potential factors associated with insomnia in patients with end-stage kidney disease undergoing hemodialysis. Variables for the multivariate logistic regression analysis model were selected based on statistical significance in univariate analysis (p<0.05), clinical relevance and environment factors (age, co-morbidities, hemodialysis duration, Duration of end-stage kidney disease…). We confirm that logistic regression assumptions, including linearity of logit for continuous variables and absence of multicollinearity, were met, ensuring the model’s suitability for analysis.

    Ethics

    All clinical data were extracted from medical records. Ethics approval was obtained from the Biomedical Ethics Committee of Hue University of Medicine and Pharmacy (No H2023/403, issued 02/6/2024). This study was conducted in accordance with the principles of the Declaration of Helsinki.

    Results

    Prevalence of Insomnia According to DSM 5 Criteria Among Participants

    A total of 216 patients with end-stage kidney disease on hemodialysis, with a mean age of 56.7 (SD 14.5), 98 women (45.4%) and 118 men (54.6%), participated in the study and completed the questionnaire. Among them, 104 participants (48.1%) had insomnia, according to the DSM – 5 criteria (Table 1).

    Table 1 Prevalence of Insomnia According to DSM 5 Criteria Among Participants

    Socio-Demographic Characteristics of the Participants and Differences Between Insomnia and without Insomnia Groups

    The mean age was significantly higher in the insomnia group than in the non-insomnia group (p=0.03) (Table 2). While mean age was higher in the insomnia group (p=0.03), age as a categorical variable (<60 vs ≥60) was not significantly associated with insomnia (p=0.18), suggesting age-related risk may not follow a simple dichotomous pattern. There were no significant differences between the insomnia and non-insomnia groups in terms of sex, education level, marital status, and job status (p>0.05).

    Table 2 Socio-Demographic Characteristics of the Participants and Differences Between Insomnia and Without Insomnia Groups

    Clinical and Laboratory Characteristics Associated with Insomnia Among Participants

    The results in Table 3 show that the duration of end-stage kidney disease and hemodialysis in the group with insomnia were significantly longer than those in the group without insomnia (p=0.01 and 0.02, respectively). Other clinical and laboratory factors were not associated with insomnia in the study subjects.

    Table 3 Clinical and Laboratory Characteristics Associated with Insomnia Among Participants

    Co-Morbidities Associated with Insomnia Among the Participants

    Among the co-morbidities, only diabetes was associated with insomnia (p=0.047) (Table 4).

    Table 4 Co-Morbidities Associated with Insomnia Among the Participants

    Health Behaviors and Other Factors Associated with Insomnia Among Study Subjects

    Daytime napping and many light/noisy bedrooms were associated with insomnia, with p<0.01 and p=0.02, respectively (Table 5).

    Table 5 Health Behaviors and Other Factors Associated with Insomnia Among Study Subjects

    Factors Associated with Insomnia Through Multivariate Logistic Regression Analysis Model

    A history of diabetes (OR=0.331 for no diabetes, 95% CI: 0.148–0.738, p<0.01) and nap during the day (OR= 2.212, 95% CI: 1.159–3.885, p=0.02) and too many light/noisy bedrooms (OR= 0.051, 95% CI: 0.074–0.854 for no exposure, p=0.03) were independently associated with insomnia (Table 6).

    Table 6 Factors Associated with Insomnia Through Multivariate Logistic Regression Analysis Model (Only Variables That Were Significant in the Univariate Analysis (P<0.05) From Table 3 and 5 Were Selected for Inclusion in the Multivariate Analysis)

    Discussion

    Prevalence of Insomnia

    Previous studies have shown that the prevalence of insomnia is high among patients with end-stage kidney disease undergoing hemodialysis.3–6,13 The findings of this study showed that prevalence of insomnia according to DSM 5 criteria was 48.1% among patients with hemodialysis (Table 1). Our study focused exclusively on assessing insomnia disorder based on the clinical criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), without evaluating other sleep disorders. Additionally, due to resource constraints, this study did not employ objective sleep assessment methods, such as polysomnography. To address this limitation, we implemented a rigorous diagnostic process involving two independent psychiatrists to evaluate insomnia disorder. In cases of diagnostic disagreement, a third independent psychiatrist was consulted to reassess, ensuring high inter-rater reliability (Cohen’s Kappa, κ=0.85). This approach enhanced the accuracy and consistency of our diagnoses, compensating for the absence of objective measures. Despite these efforts, the reliance on clinical assessments alone may limit the generalizability of our findings. Future studies could incorporate polysomnography or actigraphy to validate clinical diagnoses and explore other sleep disorders in hemodialysis patients. By focusing on DSM-5 criteria, our study contributes to the literature by providing a robust clinical perspective on insomnia disorder prevalence and associated factors in this understudied population in Vietnam. The prevalence of insomnia among patients with end-stage kidney disease undergoing hemodialysis varies widely across countries and studies. Tan et al performed a meta-analysis of 93 out of 3808 articles on the same topic and found that the pooled rate of insomnia among patients with chronic kidney disease undergoing hemodialysis was 46%.14 Lufiyani et al studied 125 patients with end-stage kidney disease undergoing hemodialysis in Jakarta, Indonesia realized that prevalence of insomnia was 56%. Insomnia was assessed using the Insomnia Severity Index (ISI).12

    Sabbatini M studied 694 patients undergoing hemodialysis using a specific questionnaire and found that 311 patients, accounting for 45%, complained of sleep disorders.15 Tomita et al investigated 138 patients undergoing hemodialysis found that the prevalence of insomnia, assessed the Japanese version of Pittsburgh Sleep Quality Index (PSQI), was 54.3%.11 Rai M. conducted a study of 69 outpatients undergoing maintenance hemodialysis in India, the results showed that the prevalence of insomnia by a battery of questions was 60.9%.16 In Vietnam, Phan et al’s study showed that prevalence of insomnia by PSQI was 66.4% among 68 patients undergoing hemodialysis at Viet Duc Hospital, Hanoi, Vietnam.3 The difference in the prevalence of insomnia among studies was due to the use of different assessment tools. Most studies used scales such as the ISI, PSQI, and specific questionnaires for assessment, and our study used the clinical criteria of DSM 5 to assess insomnia, which was performed by psychiatrists.

    Associated Factors

    The mean age was significantly higher in the insomnia group than in the non-insomnia group (p =0.03) (Table 2). However, age was no longer an independent factor associated with insomnia in the study participants when analysed using multivariate regression (Table 6). The association between age and insomnia in dialysis patients is inconsistent. Some studies suggest that older age increases the risk of insomnia in hemodialysis patients,13,14,17,18 while other studies indicate no association between age and insomnia in dialysis patients.

    Benetou et al studied 100 patients undergoing hemodialysis in Greece and reported that age > 60 years was associated with insomnia in participants.11 In their meta-analysis, Tan et al showed that the prevalence of insomnia in group age–51–60 years and > 60 years was significantly higher than that in patients aged < 50 years.10 Velu et al also showed that patients aged > 60 years tended to have more sleep disturbances using the PSQI and ESS scales.18 However, this result is not consistent with those of other studies. Lufiyani’s study showed that age was not associated with insomnia.12 Lufiyani‘s study results were also shared by other authors such as Alkhuwaiter and Rai.16,19 This inconsistency could be explained by some reasons concluding differences in the diagnostic instruments, place of study, sample size, and other factors associated with insomnia.

    The results in Table 3 show that the duration of end-stage kidney disease and hemodialysis in the group with insomnia were significantly longer than those in the group without insomnia (p=0.01 and 0.02, respectively). Rahmad et al conducted a study of 57 dialysis patients in Indonesia and found that HD duration was positively correlated with sleep quality (p=0.006, r=0.41).20 Studies by other authors also showed that duration of hemodialysis was related to sleep disorders.16,21 Rai et al found that prevalence of insomnia among patients with duration of hemodialysis more than 1 year was significantly higher than those with duration of hemodialysis of 1 year or less (84.6% and 46.5%, respectively, p=0.003).16 This result was also confirmed in the Hamzi‘s study.21 Hamzi conducted a multicenter study from Morocco in 128 patients on hemodialysis and found that a long duration of hemodialysis was one of two risk factors of insomnia in their study.21 The long duration of chronic kidney disease and hemodialysis may be associated with complications, co-morbid diseases, tiredness, and bone pain, leading to insomnia.

    The association between laboratory test results and sleep disorders varies widely among studies. In our study, laboratory factors, including plasma urea, creatinine, hemoglobin, hematocrit, and GFR, were not associated with insomnia in the study subjects (Table 3). The results of this study are similar to those of several previous studies in patients on hemodialysis.21–24 Liu et al found a correlation between creatinine, blood urea nitrogen, and alanine transaminase (ALT) levels and sleep disorders (p<0.001),25 Hashem et al showed that plasma creatinine levels were different in good sleep and poor sleep groups among patients on hemodialysis (p<0.05).26 Koch et al studied 112 patients undergoing hemodialysis and demonstrated that an elevated level of urea was an independent variable associated with sleep disorders and hemoglobin levels between 10 and 12 g/dl were associated with better sleep quality.27 Velu et al studied 148 patients on hemodialysis and indicated that lower hemoglobin levels were associated with PSQI and ESS scores.18

    The results in Table 3 reveal that BMI, anemia, and the number of hemodialysis sessions per week were not associated with insomnia. Hamzi et al also found that BMI is not associated with insomnia.19 Sabbatini et al showed that BMI and hemoglobin concentration did not differ between insomnia and control group.15

    Our findings indicated that among comorbid diseases, only diabetes was associated with insomnia in the participants (Table 4), which continued to be an independent variable associated with insomnia in the multivariable regression analysis (Table 6). Diabetes is also associated with depression, peripheral neuropathy, and neuropathic pain. These factors may contribute to insomnia in patients undergoing hemodialysis for diabetes. Diabetes can cause insomnia and, in turn, change the patient’s mood, causing fatigue and poor blood glucose control, thereby creating a vicious cycle and possibly leading to more severe kidney failure. Therefore, these results suggest clinicians in hemodialysis settings should focus on insomnia symptoms and associated factors and consider collaboration with psychiatrists and internal medicine in other specialties to explore effective treatment strategies. Han et al studied eighty-two diabetes patients on hemodialysis for more six months from 12 hospitals found that the prevalence of insomnia in these patients was 68.2%, and depression, age, and nutrition were factors associated with insomnia among diabetic hemolysis patients.28

    In addition to pathological factors, environmental factors, sleep habits, and psychological factors have been associated with insomnia. Our results showed that patients with daytime naps had a significantly higher rate of insomnia than those without daytime naps (Table 5 and 6, p<0.05). Daytime sleepiness and insomnia are bidirectional, with insomnia leading to daytime sleepiness; conversely, daytime naps lead to insomnia or poor sleep quality at night. This association is not only observed in hemodialysis patients but also in the general population, especially in the elderly. Literature and data from previous studies in hemodialysis patients suggest that daytime napping disrupts nocturnal sleep.29,30 Ancoli et al in their review study indicated that elderly people who complained insomnia also reported more frequent daytime napping.28 Al – Jahdali et al reported that daytime sleepiness was one of the factors associated with insomnia in 227 patients undergoing hemodialysis at two centers in Saudi Arabia.30 The results in Table 5 and 6 show that sleep was also affected by exposure with excessive bright and noisy environments. These factors were not specific to hemodialysis patients but were associated with insomnia in the general population. Literature and data have confirmed that sleep hygiene education, by decreasing exposure to light or noise in the environment, could promote healthy sleep habits.31,32 Tao et al conducted an intervention program on 105 hemodialysis patients aged 45 years and older with poor sleep quality assessed by the PSQI scale using sleep hygiene education that emphasized reducing exposure to light and noise along with relaxation techniques, and found significant improvement in sleep quality after 12 weeks.31 Abdelkader et al revealed that environmental factors, including excessive light, noise at home, and relative movement, are associated with sleep disorders in hemodialysis patients.32

    Our study identified diabetes mellitus, duration of hemodialysis, daytime napping, and exposure to excessive noisy/light bedrooms as significant factors associated with insomnia among patients with end-stage kidney disease on hemodialysis. Diabetes mellitus was independently associated with insomnia (OR=0.331 for no diabetes, 95% CI: 0.148–0.738, p<0.01), potentially due to its contribution to peripheral neuropathy and neuropathic pain, which disrupt sleep initiation and maintenance through heightened sensory discomfort.28 Longer duration of hemodialysis (p=0.02 in univariate analysis) may exacerbate insomnia through cumulative uraemic toxin exposure and physical fatigue, which increase central nervous system irritability and sleep fragmentation.19 Daytime napping (OR=2.122, 95% CI: 1.159–3.885, p=0.02) was strongly associated with insomnia, likely because it disrupts the circadian rhythm, reducing nocturnal sleep drive, a mechanism well documented in hemodialysis populations and the elderly.28 Similarly, excessive noisy or light bedrooms (OR=0.251 for no exposure, 95% CI: 0.074–0.854, p=0.03) likely impair sleep by increasing arousal and disrupting sleep consolidation, consistent with findings that environmental factors exacerbate sleep disturbances in hemodialysis patients.31 These results align with global studies but highlight a higher insomnia prevalence (48.1%) in our Vietnamese cohort compared to some Western studies,15 possibly due to limited access to sleep hygiene education or mental health support in Vietnam, emphasizing the need for culturally tailored interventions.

    Our results demonstrated that health behaviors and other factors, including smoking, alcohol consumption, use of electronic devices before bedtime, and stressful events/conflicts in the last three months, were not associated with insomnia. Several previous studies have reported similar results to ours.15,25,30

    The strengths of our study were that first, we used the DSM 5 clinical criteria to diagnose insomnia, and the diagnoses were made by psychiatrists who were not involved in the study, second, the comprehensive and exhaustive collection of variable data. The inclusion of a wide range of clinical, behavioral, and laboratory factors enables a more comprehensive analysis of potential contributors to insomnia, thereby strengthening the validity of the multivariate findings.

    However, our study has some limitations: first, it was a cross-sectional study, so it is difficult to determine the causal relationship of factors with insomnia; second, our study is not a multicenter study, which limits the generalizability of the findings to broader or more diverse hemodialysis populations. Third, convenience sampling may introduce selection bias, as recruited patients may not represent the broader hemodialysis population. Besides, there are some factors that may be related to insomnia but were not examined in our study such as the medications used by the patient, serum phosphate level. Restless leg syndrome, previously reported to contribute to poor sleep quality in hemodialysis patients,22 was not assessed in this study but is an important direction for future research.

    Conclusion

    The prevalence of insomnia was high (48.1%) among Vietnamese patients with chronic kidney diseases on hemodialysis, consistent with global estimates of 30–80%. Multivariate logistic regression analysis revealed several factors associated with insomnia, including a history of diabetes mellitus, naps during the day, and exposure to excessive light or noise bedrooms.

    Given the high prevalence of insomnia among patients undergoing hemodialysis, awareness of insomnia among these patients should be raised among nephrologists and internal medicine doctors. Screening patients on hemodialysis for co-morbid insomnia with using standardized tools like The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and its risk factors and consider collaboration with psychiatrists to explore treatment strategies is also recommended. To improve this study’s limitations, I suggested that future studies should employ objective sleep measures, explore medication effects, serum phosphate level and investigate interventions targeting identified factors.

    Data Sharing Statement

    The data supporting the findings of this study are available upon request from the corresponding author.

    Acknowledgment

    The authors wish to thank the patients and the hospital staff who participated and facilitated us in this study.

    Funding

    This study did not receive any funding.

    Disclosure

    The authors have no conflict of interest to declare in this work.

    References

    1. American Psychiatric Association. Diagnostic and Statistical of Mental Disorders. 5th, Edition. Washington, DC: APA; 2013.

    2. Lindner AV, Novak M, Bohra M, et al. Insomnia in patients with chronic kidney disease. Semin Nephrol. 2015;35(4):14. doi:10.1016/j.semnephrol.2015.06.007

    3. Thành PT. Khảo sát rối loạn giấc ngủ của bệnh nhân thận nhân tạo chu kỳ, Nội khoa, Đại học Y Hà Nội, Luận văn Thạc sỹ y học. 2019

    4. Ezzat H, Mohab A. Prevalence of sleep disorders among ESRD patients. Ren Fail. 2015;37(6):1013–1019. doi:10.3109/0886022X.2015.1044401

    5. Lufiyani I, Zahra AN, Yona S. Factors related to insomnia among end-stage renal disease patients on hemodialysis in Jakarta, Indonesia. Enferm Clin. 2019;29(S2):5. doi:10.1016/j.enfcli.2019.04.141

    6. Al-Ali F, Elshirbeny M, Hamad A, et al. Prevalence of depression and sleep disorders in patients on dialysis: a cross-sectional study in Qatar. Int J Nephrol. 2021;2021:5533416. doi:10.1155/2021/5533416

    7. Naragaki Y, You AS, Kurtz I, et al. Sleep patterns, symptoms, and mortality in hemodialysis: a prospective cohort study. Kidney Med. 2025;7(4):100976. doi:10.1016/j.xkme.2025.100976

    8. Li Q, Xia F, Wang G, Chen R, Chen G. Effect of mental state on sleep quality in patients receiving maintenance hemodialysis: a multiple mediation model of hope and family function. Medicine. 2024;103(45):e40503. doi:10.1097/MD.0000000000040503

    9. Ye W, Wang L, Wang Y, et al. Depression and anxiety symptoms among patients receiving maintenance hemodialysis: a single center cross-sectional study. BMC Nephrol. 2022;23(1):417. doi:10.1186/s12882-022-03051-8

    10. Nagy E, Tharwat S, Elsayed AM, Shabaka SAE, Nassar MK. Anxiety and depression in maintenance hemodialysis patients: prevalence and their effects on health-related quality of life. Int Urol Nephrol. 2023;55(11):2905–2914. PMID: 37009953; PMCID: PMC10560136. doi:10.1007/s11255-023-03556-7

    11. Tomita T, Yasui-Furukori N, Oka M, et al. Insomnia in patients on hemodialysis for a short versus long duration. Neuropsychiatr Dis Treat. 2016;12:2293–2298. doi:10.2147/NDT.S106819

    12. Lufiyani I, Zahra AN, Yona S. Factors related to insomnia among end-stage renal disease patients on haemodialysis in Jakarta, Indonesia, the second international nursing scholar congress (INSC 2018) of faculty of nursing. University Indonesia. 2019;29(2):331–335.

    13. Almutary H. Fatigue and pruritus impact sleep quality in hemodialysis patients. Nat Sci Sleep. 2024;16:2289–2298. doi:10.2147/NSS.S496376

    14. Tan LH, Chen PS, Chiang HY, et al. Insomnia and poor sleep in CKD: a systematic review and meta-analysis. Kidney Med. 2022;4(5):100458. doi:10.1016/j.xkme.2022.100458

    15. Sabbatini M, Minale B, Crispo A, et al. Insomnia in maintenance haemodialysis patients. Nephrol Dial Transplant. 2002;17(5):852–856. PMID: 11981073. doi:10.1093/ndt/17.5.852

    16. Rai M, Rustagi T, Rustagi S, Kohli R. Depression, Insomnia and sleep apnea in patients on maintenance haemodialysis. Indian J Nephrol. 2011;21(4):223–229. doi:10.4103/0971-4065.83028

    17. Benetou S, Alikari V, Vasilopoulos G, et al. Factors associated with insomnia in patients undergoing haemodialysis. Cureus. 2022;14(2):e22197. PMID: 35308769; PMCID: PMC8925937. doi:10.7759/cureus.22197

    18. Velu S, Rajagopalan A, Arunachalam J, Prasath A, Durai R. Subjective assessment of sleep quality and excessive daytime sleepiness in conventional hemodialysis population: a single-center experience. Int J Nephrol Renovascular Dis. 2022;Volume 15:103–114. doi:10.2147/IJNRD.S351515

    19. Alkhuwaiter RS, Alsudais RA, Ismail AA. A prospective study on prevalence and causes of insomnia among end-stage renal failure patients on haemodialysis in selected dialysis centers in Qassim, Saudi Arabia. Saudi J Kidney Dis Transpl. 2020;31(2):454–459. doi:10.4103/1319-2442.284021

    20. Rahmad MN, Sutarman S, Kanita MW, et al. The relationship between the hemodialysis span and the stress level and sleep quality of chronic kidney failure patients in hemodialysis room at Tk. III slamet Riyadi hospital Surakarta. J Midwifery Nursing. 2024;6(2):591–596. doi:10.35335/jmn.v6i2.4322

    21. Hamzi MA, Hassani K, Asseraji M, El Kabbaj D. Insomnia in hemodialysis patients: a multicenter study from Morocco. Saudi J Kidney Dis Transpl. 2017;28(5):1112–1118. doi:10.4103/1319-2442.215152

    22. Xu N, Li S, Zhang X, et al. Restless legs syndrome in end-stage renal disease patients on maintenance hemodialysis: quality of life and sleep analysis. Adv Neuro. 2023;X(X):1–10.

    23. Chu G, Suthers B, Moore L, et al. Risk factors of sleep-disordered breathing in haemodialysis patients”. PLoS One. 2019;14(8):1–11. doi:10.1371/journal.pone.0220932

    24. Zhao Y, Zhang Y, Yang Z, et al. Sleep disorders and cognitive impairment in peritoneal dialysis: a multicenter prospective cohort study. Kidney Blood Pressure Res. 2019;44(5):1115–1127. doi:10.1159/000502355

    25. Liu Z-H. Evaluation of risk factors related to sleep disorders in patients undergoing hemodialysis using a nomogram model”. Medicine. 2024;103:1–6.

    26. Hashem RES, Abdo TA, Sarhan II, et al. Sleep pattern in a group of patients undergoing hemodialysis compared to control”. Middle East Curr Psychiatr. 2022;29(3):1–8. doi:10.1186/s43045-021-00168-8

    27. Koch BC, Nagtegaal JE, Hagen EC, et al. Subjective sleep efficiency of hemodialysis patients. Clin Nephrol. 2008;70(5):411. doi:10.5414/CNP70411

    28. Han SY, Yoon JW, Jo S-K, et al. Insomnia in diabetic hemodialysis patients: prevalence and risk factors by a multicenter study. Nephron. 2002;92(1):127–132. doi:10.1159/000064460

    29. Ancoli SL, Martin JL. insomnia and daytime napping in older adults. J Clin Sleep Med. 2006;2:333–342.

    30. Al-Jahdali HH, Khogeer HA, Al-Qadhi WA, et al. Insomnia in end-stage kidney patients on dialysis in Saudi Arabia. J Circadian Rhythms. 2010;8:Art.7. doi:10.1186/1740-3391-8-7

    31. Tao LL, Zeng CH, Mei WJ, Zou YL. Sleep quality in middle-aged and elderly hemodialysis patients: impact of a structured nursing intervention program. World J Clin Cases. 2024;12(25):5713–5719. PMID: 39247744; PMCID: PMC11263055. doi:10.12998/wjcc.v12.i25.5713

    32. Abdelkader HM, Elsaida Gamal Aly Boghdady EG, El-sehrawy AE. Factors affecting sleep pattern disturbance for hemodialysis patients in port said hospitals. Port Said Scientific J Nursing. 2023;10(4):1–22.

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  • Should Chest CT be Routine for Prostate Cancer Patients on Androgen Deprivation Therapy?

    Should Chest CT be Routine for Prostate Cancer Patients on Androgen Deprivation Therapy?

    For patients receiving androgen deprivation therapy (ADT) for prostate cancer (PCa), emerging research affirms that assessing myocardial extracellular volume (ECV) from chest contrast-enhanced computed tomography (CECT) may provide significant utility in monitoring for cardiotoxicity and predicting major adverse cardiovascular events (MACEs).

    In a retrospective study, recently published in the European Journal of Radiology, researchers evaluated CECT-derived ECV at baseline and at three, six, nine and 12 months after the initiation of ADT in 180 patients (median age of 70 at first chest CECT) with PCa. Twenty-four percent of the cohort (44 patients) developed MACE, according to the study.

    Overall, the study authors noted a significant increase in myocardial ECV three months after ADT initiation (27.93 percent) in comparison to baseline assessment (23.45 percent). However, there was no change in the left ventricular ejection fraction (LVEF) at three months (68.5 percent) and a slight decrease at 12 months (67 percent) after ADT initiation.

    Here one can see unenhanced and enhanced CT images showing CT values of the left ventricle and ventricular septum at baseline and at three, six and nine months after administration of androgen deprivation therapy (ADT) for a 66-year-old patient with major adverse cardiovascular events (MACE). (Images courtesy of the European Journal of Radiology.)

    “The study results showed that myocardial ECV was gradually increased and LVEF was gradually decreased in PCa patients after receiving ADT, which indicates that ADT is indeed cardiotoxic. The difference between the MACE (+) and MACE (−) groups was statistically significant after 3 months of ADT, but there was no difference in LVEF between the two groups. This proves that myocardial ECV can detect ADT-induced cardiotoxicity earlier than LVEF,” wrote lead study author Xinyu Zhang, M.D., who is affiliated with the Department of Radiology at the Chongqing University Cancer Hospital and Chongqing Cancer Institute in Chongqing, China, and colleagues.

    While acknowledging a lack of statistically significant changes at six and nine months, the researchers pointed out that myocardial ECV was nearly 10 percent higher one year after patients started ADT (33.71 percent).

    The study authors noted that patients who had MACE had higher myocardial ECV at three, six, nine and 12 months in contrast to patients who did not develop MACE. One year after ADT initiation, those in the MACE cohort had a mean myocardial ECV of 38.80 percent in comparison to 32.06 percent in the non-MACE group.

    Three Key Takeaways

    1. Myocardial ECV detects early cardiotoxicity from ADT. CECT-derived myocardial extracellular volume increased significantly within three months of ADT initiation, preceding measurable changes in LVEF, suggesting ECV is a more sensitive early marker of ADT-related cardiotoxicity.
    2. Higher ECV predicts major adverse cardiovascular events (MACE). Patients with elevated myocardial ECV had a significantly higher risk of MACE at three, six, and nine months, with risk increasing over time compared to those with lower ECV.
    3. Clinical utility for monitoring PCa patients on ADT. Serial CECT-derived myocardial ECV measurements may provide a practical tool for early detection and risk stratification of cardiotoxicity in prostate cancer patients receiving ADT, potentially guiding closer cardiovascular surveillance and management.

    Patients with high ECV had a 2.695-fold higher risk of MACE at three months, a 3.670-fold higher risk at six months and a 4.450-fold higher risk at nine months in contrast to those with lower ECV, according to the researchers.

    “In the future, if more prospective studies can confirm the ability of myocardial ECV derived from chest CECT to predict MACE, it may be the basis for routine chest CECT examination in PCa patients receiving ADT,” posited Zhang and colleagues.

    (Editor’s note: For related content, see “Study Examines Potential of Ultra-high Spatial Resolution Photon-Counting CT for Coronary Plaque Quantification,” “The Reading Room Podcast: Emerging Trends with Theranostics in Prostate Cancer, Part 2” and “Multimodal AI with CCTA and MRI Data Shows Promise in Predicting MACE in Patients with Obstructive CAD.”)

    Beyond the inherent limitations of a single-center retrospective study, the authors acknowledged a lack of comparison of cardiotoxic effects for different classes of castrating drugs. They also conceded a lack of cardiac biopsies for patients with MACE and the exclusion of patients who died from non-cardiovascular causes during the follow-up period of the study.

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  • Use of rocuronium during ophthalmic surgery is associated with less in

    Use of rocuronium during ophthalmic surgery is associated with less in

    Shao-Chun Wu,1– 3,&ast; Jo-Chi Chin,4,&ast; Kuo-Chuan Hung,3,5 Chih-Yi Hsu,3 Yung-Fong Tsai,2,6 Amina M Illias2,6

    1Department of Anaesthesiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; 4Department of Anaesthesiology, Kaohsiung Show Chwan Memorial Hospital, Kaohsiung, Taiwan; 5Department of Anaesthesiology, Chi Mei Medical Centre, Tainan, Taiwan; 6Department of Anaesthesiology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Correspondence: Amina M Illias, Department of Anaesthesiology, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan, Tel +886-975366367, Email [email protected]

    Purpose: Serious complications may arise during the onset and management of intraoperative bradycardia. This study aimed to investigate several factors that may reduce the incidence of intraoperative bradycardia in adult patients undergoing general anaesthesia for various ophthalmic procedures.
    Patients and Methods: A total of 947 adult patients who underwent general anaesthesia for different ophthalmic surgeries in 2020 were initially included. Following the exclusion of 104 cases, 843 patients were eligible for analysis. Patients received either cisatracurium with neostigmine (n = 388) or rocuronium with sugammadex (n = 455) as neuromuscular blocking and reversal agents, respectively. Quantitative neuromuscular monitoring was applied in all cases, while depth of anaesthesia was monitored using the bispectral index (BIS) in selected cases. The primary outcome was the incidence of intraoperative bradycardia, defined as a heart rate of fewer than 60 beats per minute.
    Results: The group receiving rocuronium and sugammadex demonstrated a significantly lower incidence of intraoperative bradycardia (p < 0.001). This reduction was further supported by logistic regression analysis, both in univariate (OR, 0.07; 95% CI, 0.02– 0.24; p = 0.001) and multivariate models (OR, 0.08; 95% CI, 0.02– 0.94; p = 0.001). Additionally, this group exhibited a significantly higher rate of BIS monitoring during surgery, alongside a significant reduction in total opioid (p = 0.039) and sevoflurane consumption (p < 0.001).
    Conclusion: The use of rocuronium is associated with a significant reduction in the incidence of intraoperative bradycardia in adult patients undergoing ophthalmic surgery under general anaesthesia.

    Introduction

    The typical normal adult resting heart rate (HR) is around 60–100 beats per minute (bpm) and bradycardia is mostly identified as a condition where the HR drops below 60 bpm.1,2 Intraoperative bradycardia could be induced by many factors including: the stimulation of certain nerves or reflexes and the use of certain medications during anaesthesia.3 Bradycardia during ophthalmic surgery, specifically strabismus surgery, is commonly caused by the oculocardiac reflex. Oculocardiac reflex is triggered by trigeminal nerve stimulation around the orbit or tension on an extraocular muscle tendon.4,5 Moreover, anaesthesia protocol and intraoperative medications have been reported to have significant influence on oculocardiac reflex.6 During general anaesthesia for strabismus surgery, oculocardiac reflex was increased with certain opioids such as remifentanil and hydromorphone, dexmedetomidine, dexamethasone, and hypercapnia. Additionally, when compared between six different muscle relaxants, oculocardiac reflex was increased with rocuronium.6

    The best way to treat oculocardiac reflex-induced bradycardia is by immediate cessation of the stimulus that triggers the reflex.4 This involves releasing the traction on the eyeball or removing the instrument that is causing compression on the eyeball. Once the stimulus is removed, bradycardia or cardiac arrest associated with the reflex should resolve. Anticholinergic drugs such as atropine and glycopyrrolate were equally able to prevent oculocardiac reflex with subsequent increase in HR.7 Prompt treatment of significant bradycardia is essential because untreated significant bradycardia leads to the development of cardiac arrest, hypotension and organ dysfunction.2,8 Nevertheless, potentially life-threatening conditions were reported as a consequence of attempts to treat oculocardiac reflex-induced bradycardia.9,10

    To avoid complications related to oculocardiac reflex and its treatment, it is essential to investigate the association between anaesthesia-related factors and drugs with the risk of developing intraoperative bradycardia. In this study, we compared between 2 groups of patients who received either cisatracurium or rocuronium as the neuromuscular blocking agent during general anaesthesia for different types of ophthalmic surgery. We assessed the increased incidence of intraoperative bradycardia with several anaesthesia factors, including the type of neuromuscular blocking agent, the intraoperative use of bispectral index (BIS) monitoring, along with the amount of intraoperative fluid, opioids, and sevoflurane consumption.

    Materials and Methods

    Patient Selection

    This study was approved by the Kaohsiung Chang Gung institutional review board (IRB No. 202301421B0) and the research registry identifying number can be found at https://www.researchregistry.com/browse-the-registry, Research Registry #9684. The requirement for a written or verbal informed consent was waived due to the retrospective nature of the study. Data were anonymized and maintained with confidentiality to ensure the privacy of all participants. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational studies have been applied in this retrospective observational study.11

    A total of 947 patients received general anaesthesia for different types of ophthalmic surgery throughout 2020. None of the patients had pacemaker implantation or arrhythmia on preoperative evaluation. Patients’ available medical records at our centre from January 2020 to December 2024 were further reviewed and patients other than covid-19 positive or asystole were excluded if HR less than 60 bpm was detected on 12-lead echocardiography (ECG). We did not review what medications the patients were receiving preoperatively. We excluded 104 patients: fifteen with missing data (recorded HR of less than 60 bpm before operation but with no available preoperative 12-lead ECG) and 89 patients were under 18 years of age. Finally, 843 patients were enrolled in the analysis.

    Anaesthesia and Intraoperative Monitoring

    Patients were divided into two study groups. One group received rocuronium for neuromuscular blockade and was later administered sugammadex to reverse the neuromuscular blocking effect caused by rocuronium (n = 455); and the second group received cisatracurium for neuromuscular blockade and later neostigmine as a reversal agent (n = 388) (Figure 1). In all patients, intravenous fentanyl 2 mcg kg−1 and propofol 2 mg kg−1 were used for induction of general anaesthesia and sevoflurane was used for maintenance. Patients with intraoperative BIS monitoring, BIS value was maintained between 40 and 60 to ensure adequate depth of anaesthesia. Patients did not receive any prophylactic anticholinergics during the induction or maintenance of anaesthesia.

    Figure 1 Flow diagram of participants.

    Abbreviations: HR, Heart rate; bpm, beat per minute; ECG, echocardiography.

    Quantitative neuromuscular monitoring was utilized in all cases (E-NMT Module, GE Healthcare, USA). To facilitate endotracheal intubation, cisatracurium 0.2 mg kg−1 or rocuronium 0.6–1.2 mg kg−1 were used during the induction of anaesthesia. The trachea was intubated after loss of all four twitches and train-of-four (TOF) count dropped to 0. Maintenance of paralysis during anaesthesia was achieved by redosing with an intravenous bolus of 0.03 mg kg−1 cisatracurium or 0.2 mg kg−1 rocuronium each time a TOF count equals or exceeds 2. At the end of anaesthesia, neuromuscular blocking with cisatracurium was reversed with neostigmine 0.05 mg kg−1; while rocuronium was antagonized with sugammadex 2 mg kg−1. Atropine 0.02 mg kg−1 was mixed with neostigmine to minimize the cholinergic side effects of neostigmine. Tracheal extubation was attempted only after the TOF ratio reached > 0.9.

    Objectives and Outcomes

    Some ophthalmic surgeries tend to have higher risk of developing bradycardia as reported in previous literatures.4 In this study, based on our experience and the degree of intraoperative extraocular muscle tension and stretch, we classified: eyeball surgery, keratoplasty, nasolacrimal duct surgery and orbital surgery as ophthalmic surgeries associated with less incidence of bradycardia (n = 172). Whereas pars plana vitrectomy, scleral buckling and strabismus surgery were considered as ophthalmic surgeries associated with more incidence of bradycardia (n = 671).

    The primary outcome was the incidence of bradycardia during surgical manipulation over eye area. Heart rate less than 60 bpm was considered as bradycardia in this study. Once an HR under 60 bpm was detected, surgeons were asked to stop all surgical manipulation immediately and intraoperative ECG was monitored for at least 1 minute before resuming the surgery. Atropine 1 mg was prepared as a rescue drug for any sustained or worsening significant bradycardia with HR of 40 bpm or less that lasts even after cessation of surgical manipulation.

    Statistical Analyses

    Categorical variables are presented as raw numbers or percentages. Chi-squared or Fisher’s exact test was used to compare the groups. The normality of the distribution of data was tested with the Kolmogorov–Smirnov test. Data within normal distribution were analysed with Student’s t-test and presented as mean (± standard deviation). For not normally distributed data, Mann–Whitney U-test was used for analysis and the results were presented as median (± interquartile range).

    Ten variables were used for univariate and multivariate logistic regression analysis, including gender, age, body weight, ASA, along with the use of BIS and rocuronium, the amount of intraoperative fluid, sevoflurane, and opioids, as well as the type of ophthalmic surgery according to risk of developing bradycardia. We estimated the total sample size using G*Power,12 version 3.1.9.7: with multiple linear regression analysis of the previously mentioned 10 variables used for logistic regression analysis, effect size = 0.15, α = 0.05, power = 0.95, resulting in a total sample size of 172. A total of 843 patients were enrolled in the study and assigned to 2 comparison groups comprising 388 and 455 patients, respectively. Therefore, the total number of patients in this study is far beyond the estimated total sample size.

    Results

    Study Population and Patient Characteristics

    After excluding 104 patients from a total of 947 patients, the number of patients enrolled in this study was 843. The cisatracurium and neostigmine group had 388 patients, while 455 patients were in the rocuronium and sugammadex group (Figure 1). Patient characteristics including sex, body weight, American Society of Anaesthesiologists physical status classification (ASA), comorbidity index, Apfel score, hypertension, diabetes mellitus, and cerebrovascular accident, all had no significant differences between the 2 study groups (Table 1). The median age of 60 years (52–67) for patients in the rocuronium and sugammadex group was higher than the median age of 55years (43–66) in the cisatracurium and neostigmine group.

    Table 1 Patient Characteristics

    In both groups, a significantly higher number of cases underwent ophthalmic surgeries that had relatively increased risk of bradycardia.

    Incidence of Intraoperative Bradycardia

    Several variables during anaesthesia and perioperative care are listed in Table 2. There were no significant differences in the: duration of anaesthesia, intraoperative amount of fluid infused, tracheal extubation time, the incidence of postoperative nausea and vomiting (PONV) and the total days of hospitalisation between the cisatracurium with neostigmine group and the rocuronium with sugammadex group (Table 2). When compared to the cisatracurium and neostigmine group, the rocuronium and sugammadex group had significantly lower incidence of intraoperative bradycardia. The total amount of opioid consumption (converted into morphine milligram equivalents (MME)), and the amount of sevoflurane consumption were significantly reduced in the rocuronium and sugammadex group. The intraoperative use of BIS monitoring was significantly higher in the rocuronium and sugammadex group. Interestingly, there was no significant difference in the incidence of bradycardia during ophthalmic surgeries with higher risk of developing bradycardia and those with lower risk of developing bradycardia (Table 3).

    Table 2 Anaesthesia and Perioperative Care

    Table 3 Comparison of Incidence of Bradycardia in Different Ophthalmic Surgeries

    Univariate and multivariate logistic regression model was built to analyse the association of risk variables with the incidence of intraoperative bradycardia (Table 4). In univariate analysis, the use of BIS monitoring was associated with a significant reduction in development of bradycardia. (OR 0.27; 95% CI: 0.13–0.55; p< 0.001). However, in multivariate analysis using BIS had no direct impact on the incidence of intraoperative bradycardia (p = 0.554). The rocuronium and sugammadex group had significantly lower risk of bradycardia on univariate analysis (OR 0.07; 95% CI: 0.02–0.24; p <0.001). This significant decrease in the incidence of intraoperative bradycardia with the use of rocuronium was also confirmed by multivariate analysis (OR 0.08; 95% CI: 0.02–0.94; p <0.001). Sex, age, body weight and ASA physical status, and the amount of intraoperative fluid, sevoflurane and opioids had no significant influence on the incidence of bradycardia.

    Table 4 Univariate and Multivariate Logistic Regression to Evaluate the Risk of Bradycardia (n = 843)

    Discussion

    In this retrospective single-centre study, we analysed the association between several variables and the incidence of bradycardia during surgical manipulation in various types of ophthalmic surgeries. The use of rocuronium was associated with a significant reduction in the incidence of intraoperative oculocardiac reflex-induced bradycardia.

    Researchers have defined oculocardiac reflex and bradycardia in many different ways.5,13 In this study we defined bradycardia as HR less than 60 bpm.1 Bradycardia during oculocardiac reflex could be associated with severe and possibly fatal complications.2,8,14,15 It is also important to note that while most cases of oculocardiac reflex are self-limited; the condition can potentially lead to significant morbidity and mortality, particularly during eye muscle surgery.16–18 Bradycardia can be prevented by the administration of adequate doses of anticholinergic drugs such as atropine and glycopyrrolate.7 However, treatment with anticholinergics like atropine is warranted; especially in patients who are susceptible to myocardial ischemia as a result of tachycardia and increased myocardial oxygen demand.4,9,10,16,18,19 Consequently, it is important to search for anaesthetic agents or strategies that could be associated with reduced incidence of bradycardia during ophthalmic surgeries without relying on perioperative use of anticholinergics.

    Previous studies have addressed that anaesthesia protocol and anaesthetic agents have a significant influence on oculocardiac reflex.6 Intraoperative use of certain opioids, dexmedetomidine and dexamethasone were associated with augmented oculocardiac reflex;5,6,20–22 whereas ketamine infusion was reported to decrease oculocardiac reflex.23

    Rocuronium has mild vagolytic effects that could increase HR specially when administered in large doses.24,25 It has been reported that the administration of rocuronium during ophthalmic surgery did not reduce the incidence of bradycardia; however, it was associated with less occurrence of intraoperative arrhythmias such as: supraventricular and ventricular premature beats.26 In a recent observational study, when compared to several other muscle relaxants, rocuronium was associated with more incidence of oculocardiac reflex.6 However in our study, patients who received rocuronium had significantly lower incidence of intraoperative bradycardia than patients in the cisatracurium and neostigmine group. We could think of 2 possible explanations for the reason why rocuronium was associated with decreased incidence of bradycardia in our current study while it was found to have no effect on the reduction of bradycardia in the previous 2 studies by Arnold et al6 and Karanovic et al.26 Firstly, the definition of bradycardia in different studies was not the same. Bradycardia was defined as the percentile reduction of HR in the previous two studies; while in our current study bradycardia was considered a constant, as an HR less than 60 bpm during surgical manipulation over the eyes. Patients with HR less than 60 bpm were excluded from this study. We did not investigate if patients with basic lower heart rate are subject to bradycardia after surgical manipulation. Therefore, further studies are needed to clarify this last concern. Secondly, the variation in anaesthesia condition and agents could also contribute to the difference in result between the previous 2 studies and our study. Most elective surgeries were restricted in 2021 and 2022 due to the increased number of COVID 19 cases in Taiwan during this period. To limit any bias caused by staff adjustments, lack of training and decreased number of patients; we only included ophthalmic surgeries in adult patients during 2020 in this study. We aimed to compare between 2 groups of patients who received either cisatracurium and neostigmine or rocuronium and sugammadex as the neuromuscular blocking and reversal agents, respectively. All other factors such as the kind of anaesthetic agents administered and anaesthesia conditions were held as constant as possible. It is worth to mention that in this study rocuronium was never reversed with neostigmine and patients were divided into only two groups based on the type of neuromuscular blocking and reversal agents because rocuronium was administered along with sugammadex and BIS monitoring in a set of anaesthesia package that requires self-pay. This may also explain why significantly more patients in the rocuronium and sugammadex group used BIS monitoring.

    Interestingly, in this study and in a previous study done by our group,27 the combination of rocuronium and sugammadex was associated with less consumption of volatile agents and opioids. Here, it is not clear if rocuronium itself has any potential analgesic and anaesthetic properties that could attribute to the decreased amount of opioids and sevoflurane, leading to less bradycardia with the use of rocuronium. More importantly, the reduced incidence of intraoperative bradycardia may not be attributed to a single factor such as the use of rocuronium and sugammadex. The collective effect of multiple factors should be considered as an important determinant of the incidence of intraoperative bradycardia.

    In this study, monitoring the depth of anaesthesia with a target range for BIS value between 40 and 60 – allowed consultant anaesthetists to administer sevoflurane and opioids accordingly. Intentional deep inhalational anaesthesia was never attempted, and the total amount of sevoflurane used was not inversely proportional to the incidence of bradycardia. In previous studies, the depth of anaesthesia was influenced by many factors including patient’s age, neuromuscular blocking and the use of several other medications such as: ketamine, nitrous oxide, inhalation agents and opioids.28,29 Although BIS monitoring cannot entirely prevent intraoperative awareness,30–32 yet many other potential benefits were reported when BIS monitoring was utilized during general anaesthesia; specifically, the significant reduction in anaesthetic drug consumption and optimal enhanced recovery after surgery (ERAS).33,34 Despite the difference in anaesthesia agents and conditions such as: the use of neuromuscular blocking in some cases, the use of laryngeal mask instead of endotracheal tube, and the difference in the definition of bradycardia in each study; all previous evidence suggested that deeper anaesthesia could protect against oculocardiac reflex.13,35 However, in an era where we cannot emphasize enough on the importance of precision medicine, it would be inappropriate to increase the amount of anaesthesia agents and hence increasing the depth of anaesthesia just to prevent oculocardiac reflex without actual/digital evidence that the depth of anaesthesia is not enough for a certain surgical stimulation. Not to mention the serious consequences of unnecessary increased amount of anaesthetic agents which could lead to hemodynamic instability and burst suppression of electroencephalography (EEG).36–39 Lastly, the decrease in the total amount of opioids in the rocuronium and sugammadex group is beneficial in terms of reducing the augmentation of oculocardiac reflex by excessive use of opioids.21

    Regardless of the type of neuromuscular blocking or reversal agent used during general anaesthesia, the routine use of perioperative quantitative neuromuscular monitoring was suggested by many investigators in several publications. The use of quantitative neuromuscular monitoring could ensure sufficient neuromuscular blocking effect during the surgery and complete reversal before tracheal extubating.40–42 However it is not clear if the TOF ratio and hence the depth of neuromuscular blocking, has anything to do with the incidence of oculocardiac reflex during ophthalmic surgery.

    The primary outcome in this study was the incidence of bradycardia during surgical manipulation of the eyes. No persistent or worsening significant bradycardia was recorded after cessation of surgical manipulation. Therefore, no atropine was required to treat sustained bradycardia or cardiac arrest. Several factors were attributed to the limited incidence of persistent bradycardia and hemodynamic instability in this study, including careful selection of patients, proper monitoring of the depth of anaesthesia and neuromuscular blockade, as well as avoiding the administration of excessive anaesthetic agents and opioids. Nevertheless, vigilant consultant anaesthetists played a major role in early termination of intraoperative bradycardia by immediately warning the surgeons who in return stopped all surgical manipulation at once. This highlights the importance of continuous communication and discussion between the anaesthesia and surgical teams during surgery.13,43

    In both study groups, more surgeries with relatively increased risk of bradycardia were performed. Interestingly, when compared to ophthalmic surgeries with low risk of developing bradycardia, no significant difference was discovered in the incidence of bradycardia in ophthalmic surgeries with higher risk of developing bradycardia. This probably indicates that our surgeons have a matured skill with limited surgical stimulation that largely reduce the incidence of oculocardiac reflex.4

    Finally, we must address the potential bias inherent to retrospective studies that could interfere with the findings of this study. The generalizability of the result from this study in paediatrics and different races should be tested in a large randomized prospective trial. Indeed, it is the less likely for a single factor or a drug to be the sole determinant of decreased intraoperative bradycardia unless all variables are held constant throughout the anaesthesia and surgery. Consequently, the more factors associated with decreased oculocardiac reflex are available during anaesthesia, the less likely for an intraoperative bradycardia to occur. However, large randomized controlled clinical trials are needed to determine if one factor has a greater effect on suppressing oculocardiac reflex than another one.

    In conclusion, both consultant anaesthetist and surgeon have an influence on the incidence of bradycardia during ophthalmic surgery. The use of rocuronium was associated with a significant reduction in the incidence of bradycardia during ophthalmic surgery in adult patients. Regardless of the cause of intraoperative bradycardia, oculocardiac reflex related or not, it is important to note that the management of bradycardia and the administration of anaesthesia agents should be individualized based on each patient’s specific condition and proper clinical monitoring and evaluation. Further, randomized controlled clinical trials are essential to establish a clear connection between any suggested risk factor and the incidence of bradycardia during ophthalmic surgeries.

    Abbreviations

    ASA, American Society of Anaesthesiologists physical status classification; bpm, beats per minute; BIS, bispectral index; CI, confidence interval; ECG, echocardiography; EEG, electroencephalography; HR, heart rate; IQR, interquartile range; OR, odds ratio; TOF, train-of-four.

    Data Sharing Statement

    The data presented in this study are available from the corresponding author upon reasonable request.

    Acknowledgments

    We appreciate the statistical analyses assistance by the Biostatistics Canter, Kaohsiung Chang Gung Memorial Hospital.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    This research received no external funding.

    Disclosure

    The authors declare that they have no conflicts of interest.

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