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Cost-effectiveness of Apixaban vs Aspirin for the Reduction of Thrombo-Embolism in High-Risk Patients with Device-Detected Atrial Fibrillation: Insights from the ARTESiA trial
Full text linkBackground and Aims
Apixaban was superior to aspirin for the prevention of stroke or systemic embolism in participants with subclinical atrial fibrillation (SCAF) in the Apixaban for the Reduction of Thrombo-Embolism in Patients with Subclinical Atrial Fibrillation (ARTESiA) trial. This was especially true for those with CHA2DS2-VASc score >4. Understanding the cost-effectiveness of treating SCAF is important for decision makers.
Methods
Canadian, UK, German and US direct healthcare costs (in 2023 USD) were applied to hospitalized events (including strokes and bleeds) and study drugs for all participants with a CHA2DS2-VASc score >4 to determine the mean cost per participant during the trial (mean follow-up 3.5 years). A daily cost of 0.11, 6.06 for apixaban in Canada, UK, Germany and the US was used. If in-trial results were not cost-saving (below 2,301) and the UK (-600 and 2,623 more) and the US (24,514 per QALY for Germany and 4.35, and cost saving at $3.59
Myo‐Guide: A Machine Learning‐Based Web Application for Neuromuscular Disease Diagnosis With MRI
Full text linkBackground
Neuromuscular diseases (NMDs) are rare disorders characterized by progressive muscle fibre loss, leading to replacement by fibrotic and fatty tissue, muscle weakness and disability. Early diagnosis is critical for therapeutic decisions, care planning and genetic counselling. Muscle magnetic resonance imaging (MRI) has emerged as a valuable diagnostic tool by identifying characteristic patterns of muscle involvement. However, the increasing complexity of these patterns complicates their interpretation, limiting their clinical utility. Additionally, multi‐study data aggregation introduces heterogeneity challenges. This study presents a novel multi‐study harmonization pipeline for muscle MRI and an AI‐driven diagnostic tool to assist clinicians in identifying disease‐specific muscle involvement patterns.
Methods
We developed a preprocessing pipeline to standardize MRI fat content across datasets, minimizing source bias. An ensemble of XGBoost models was trained to classify patients based on intramuscular fat replacement, age at MRI and sex. The SHapley Additive exPlanations (SHAP) framework was adapted to analyse model predictions and identify disease‐specific muscle involvement patterns. To address class imbalance, training and evaluation were conducted using class‐balanced metrics. The model's performance was compared against four expert clinicians using 14 previously unseen MRI scans.
Results
Using our harmonization approach, we curated a dataset of 2961 MRI samples from genetically confirmed cases of 20 paediatric and adult NMDs. The model achieved a balanced accuracy of 64.8% ± 3.4%, with a weighted top‐3 accuracy of 84.7% ± 1.8% and top‐5 accuracy of 90.2% ± 2.4%. It also identified key features relevant for differential diagnosis, aiding clinical decision‐making. Compared to four expert clinicians, the model obtained the highest top‐3 accuracy (75.0% ± 4.8%). The diagnostic tool has been implemented as a free web platform, providing global access to the medical community.
Conclusions
The application of AI in muscle MRI for NMD diagnosis remains underexplored due to data scarcity. This study introduces a framework for dataset harmonization, enabling advanced computational techniques. Our findings demonstrate the potential of AI‐based approaches to enhance differential diagnosis by identifying disease‐specific muscle involvement patterns. The developed tool surpasses expert performance in diagnostic ranking and is accessible to clinicians worldwide via the Myo‐Guide online platform
Clinical care of family members of patients with dilated cardiomyopathy
Full text linkGenetic family screening following the detection of a pathogenic or likely pathogenic variant in a proband with dilated cardiomyopathy (DCM) remains one of the main applications of genetic testing. While cardiac screening is recommended for all first-degree relatives, the a priori risk among family members varies. Consequently, screening regimens should be tailored according to both genetic and clinical information at the individual and familial level. This clinical consensus statement provides tools to help with the risk assessment and follow-up of screening for family members and discusses the utility for integration of genotype-specific information, cardiac imaging, and electrocardiogram findings to personalize cardiac screening regimens, which in conjunction will likely improve individualized risk prediction. Early phenotypic detection of DCM in family members remains an active area of research and innovation. In addition, data are starting to accrue on the utility of early therapeutic intervention in family members with very mild phenotypes that may inform future management in addition to screening. A systematic strategy is proposed to determine the a priori risk of developing DCM for a family member, and the potential of integrating genotype–phenotype knowledge towards family management. Lastly, there is a focus on the current knowledge gaps and ongoing and future opportunities to improve risk prediction, early disease detection, and treatment of family members of patients with DCM
Human papillomavirus (HPV) genotype distribution in Malaysia: A systematic review
Full text linkBackground
Human papillomavirus (HPV) is a key etiological factor in cervical cancer in both Malaysia and globally. It continues to pose a significant public health challenge. This systematic review aims to delineate the distribution of HPV genotypes across different demographics in Malaysia to inform targeted prevention strategies.
Methods
We conducted a systematic review following PRISMA guidelines, analyzing observational studies published from 2000 onward that reported HPV genotypes in cervicovaginal samples from Malaysian women. The review utilized PubMed, SCOPUS, The Cochrane Library, APA PsycNet, and Google Scholar for literature searches, focusing on studies that employed molecular methods for HPV genotyping. Two reviewers independently screened the articles, extracted data, and assessed study quality using the Newcastle-Ottawa Scale (NOS). A descriptive analysis was performed, and findings were synthesized by genotype, region, and ethnicity.
Results
The review included 22 studies from an initial pool of 2,547 articles, encompassing 44,251 women. These studies reported a HPV prevalence of up to 100% in confirmed cervical cancer cases and in general screenings from 4.5 to 47.7%. A total of 28 different HPV genotypes (high- and low-risk) were identified, with HPV16, HPV18, HPV58, HPV52, and HPV33 being the most prevalent high-risk genotypes. Genotype distributions showed significant variation across different states and ethnic groups within Malaysia, highlighting the diverse nature of HPV-related risks.
Conclusions
This review provides a detailed snapshot of the HPV genotype distribution in Malaysia, underscoring the necessity for tailored public health interventions that address the regional and ethnic diversity in HPV prevalence. The findings support the need for targeted vaccination programs and enhanced screening measures to effectively combat the high rates of HPV-related (99%) cervical cancer in Malaysia
HbA1c variability and all-cause mortality in Type 1 and Type 2 diabetes: a population-based cohort study using electronic health records
Full text linkAims
To investigate associations between HbA1c variability and all-cause mortality in individuals with diabetes, accounting for average HbA1c level
Methods
Mean HbA1c and variability score (HVS) were estimated for people aged 31–90 with diabetes (type 1 = 20,347, type 2 = 409,821) with 4 + HbA1c measurements recorded in the Clinical Practice Research Datalink in 2011–14 and alive on 1/1/2015. Cox models estimated hazard ratios (HR) for all-cause mortality, ascertained from national linked mortality data during 2015–17. HbA1c level and variability were mutually adjusted for each other and other measured confounders.
Results
Greater HbA1c variability was associated with younger age, non-white ethnicities (type 1 only), obesity, co-morbidities, and living in deprived areas. During follow-up, 1,043 (5.1 %) individuals with type 1 diabetes and 40,723 (9.9 %) individuals with type 2 diabetes died. In those with the most HbA1c variability compared to the least (HVS = 80–100 vs 0–20), the estimated adjusted HRs for mortality were 2.78(95 %CI 2.15, 3.60) in type 1 diabetes and 1.91(1.83, 1.99) in type 2 diabetes.
Conclusions
Variability in HbA1c was associated with greater subsequent mortality among people living with diabetes, independent from average HbA1c. Future research should investigate whether reducing HbA1c variability over time in selected patients lowers mortality risk independent of HbA1c level improvements
Exercise Prescription in Arrhythmogenic Cardiomyopathy: Finding the Right Balance Between Risks and Benefits
Full text linkArrhythmogenic cardiomyopathy (ACM) is an inherited cardiac condition, often caused by mutations in genes encoding desmosomal proteins. The pathologic hallmark of the disease is a fibrofatty replacement of the myocardium, which constitutes the substrate for potentially fatal ventricular arrhythmias. ACM is one of the most common etiology of sudden cardiac death in athletes and young individuals. Although it is well established that regular exercise confers multiple health benefits and better survival in the general population, intense exercise may accelerate the phenotypic expression and the propensity to ventricular arrhythmias in patients with ACM. This review discusses current evidence regarding the safety and the effects of exercise in ACM. We scrutinize research findings based on animal and human models that raise concerns on the possible detrimental role of intense exercise in this condition. Finally, we examine the current knowledge on exercise prescription focusing on the optimal amount of exercise that should be recommended to patients with ACM
Providing life-sustaining treatments at home for those with Motor Neurone Disease: A qualitative study of bereaved family members' experiences of responsibility
Full text linkBackground:
Motor neurone disease is an incurable neurodegenerative condition that progressively impairs motor function. It affects mobility, speech, swallowing and breathing, leading to significant dependence on others. Home mechanical ventilation can alleviate respiratory symptoms and improve survival.
Aim:
To examine the experiences of bereaved family members involved in the care of someone with motor neurone disease who had died with home mechanical ventilation in place, or following its withdrawal.
Design:
An interpretive constructivist approach was used to carry out qualitative interviews.
Setting/participants:
Bereaved family members from England and Wales whose relative had died with ventilation in place, or after withdrawal.
Results:
Thirty-six bereaved family members took part. Their experiences highlight the extensive responsibilities and emotional burdens of managing home mechanical ventilation. Family members reported feelings of heightened responsibility, distrust in the abilities of professional caregivers, significant impacts on their mental and physical well-being and the ways in which knowledgeable care providers could lift such responsibilities.
Conclusions:
As the use of technology to sustain life increases, we need to question how much we expect of family members in providing care for those with complex interventions, such as ventilation, at home. This research underscores the critical role family members’ play in home care for people with motor neurone disease and calls for a greater understanding of the impacts of maintaining responsibility for life-sustaining treatments. There is a need for better support and training for both family and professional caregivers to alleviate some of the responsibility placed upon family members
Associations between road, rail and aircraft traffic noise with cognitive function in the UK Biobank cohort
Full text linkBACKGROUND: Studies on the associations between noise pollution and cognitive function in adults remain few. Here, we examine the cross-sectional associations between traffic noise with cognitive performance in the UK Biobank cohort. METHODS: Mid-to-older aged adults recruited during 2006-2010 were included in the analyses for road (N = 499,717), rail (N = 228,079) and aircraft (N = 105,768) noise exposures. Address-level average road noise for 2013 from minor and major roads were modelled using an enhanced CNOSSOS-EU framework; address-level average rail noise estimates for 2011 from major rail corridors were obtained from the government Department for Environment, Food and Rural Affairs; average aircraft noise estimates at postcode-level for 2011 were modelled using the ANCON model by Civil Authority Aviation for participants residing in one of 44 districts partially or wholly encompassed with weighted 24-hour day-evening-night (Lden) aircraft noise contours. Reaction time, visuospatial memory, verbal-numerical reasoning, and prospective memory were self-administered via touchscreen at baseline. Regression models were used to test associations between each traffic noise (Lden and Lnight) and each cognitive domain, allowing for covariates adjustment and correction for multiple testing. RESULTS: Exposure to higher Lnight aircraft (≥55 dB vs. <45 dB), and Lden aircraft (≥60 dB vs. <50 dB) was associated with 133 % (95 %CI: 66 %-229 %) and 48 % (95 %CI:17 %-86 %) higher error rate respectively in the visuospatial memory test; for rail Lnight and Lden, the respective figures were 68 % (95 %CI: 29 %-118 %) and 39 % (95 %CI: 10 %-75 %). There were no convincing associations of road traffic noise with visuospatial memory performance. No associations were found of reaction time, verbal-numerical reasoning, or prospective memory with any traffic-source noise. CONCLUSION: Higher aircraft and rail traffic noise exposure was associated with poorer visuospatial memory test performance, indicating a potential role in cognitive impairment in adults
Targeting Canonical Wnt-signaling Through GSK-3β in Arrhythmogenic Cardiomyopathy: Conservative or Progressive?
Full text linkArrhythmogenic cardiomyopathy is a primary myocardial disease and a major cause of sudden death in all populations of the world. Canonical Wnt signalling is a critical pathway controlling numerous processes including cellular differentiation, hypertrophy and development. GSK3β is a ubiquitous serine/threonine kinase, which acts downstream of Wnt to promote protein ubiquitination and proteasomal degradation. Several studies now suggest that inhibiting GSK3β can prevent and reverse key pathognomonic features of ACM in a range of experimental models. However, varying concerns are reported throughout the literature including the risk of paradoxical arrhythmias, cancer and off-target effects in upstream or downstream pathways
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