An endothelial contribution to coronary vessels.

Despite the profound impact of coronary artery disease on human health, the origins of the coronary blood vessels are poorly understood. Wu et al. use imaging and genetic techniques to show that the endocardium contributes to the coronary vessels and that the coronary arteries and veins have multilineage origins.

RGB Color Model: Effect of Color Change on a User in a VR Art Gallery Using Polygraph.

This paper presents computer and color vision research focusing on human color perception in VR environments. A VR art gallery with digital twins of original artworks is created for this experiment. In this research, the field of colorimetry and the application of the L*a*b* and RGB color models are applied. The inter-relationships of the two color models are applied to create a color modification of the VR art gallery environment using C# Script procedures. This color-edited VR environment works with a smooth change in color tone in a given time interval. At the same time, a sudden change in the color of the RGB environment is defined in this interval. This experiment aims to record a user's reaction embedded in a VR environment and the effect of color changes on human perception in a VR environment. This research uses lie detector sensors that record the physiological changes of the user embedded in VR. Five sensors are used to record the signal. An experiment on the influence of the user's color perception in a VR environment using lie detector sensors has never been conducted. This research defines the basic methodology for analyzing and evaluating the recorded signals from the lie detector. The presented text thus provides a basis for further research in the field of colors and human color vision in a VR environment and lays an objective basis for use in many scientific and commercial areas.

Pediatric Aerodigestive Medicine: Advancing Collaborative Care for Children With Oropharyngeal Dysphagia.

OBJECTIVES: Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients. METHODS: The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model. CONCLUSIONS: The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high-quality, and evidence-based care for patients, including those with OPD.

Toward Joint Acquisition-Annotation of Images with Egocentric Devices for a Lower-Cost Machine Learning Application to Apple Detection.

Since most computer vision approaches are now driven by machine learning, the current bottleneck is the annotation of images. This time-consuming task is usually performed manually after the acquisition of images. In this article, we assess the value of various egocentric vision approaches in regard to performing joint acquisition and automatic image annotation rather than the conventional two-step process of acquisition followed by manual annotation. This approach is illustrated with apple detection in challenging field conditions. We demonstrate the possibility of high performance in automatic apple segmentation (Dice 0.85), apple counting (88 percent of probability of good detection, and 0.09 true-negative rate), and apple localization (a shift error of fewer than 3 pixels) with eye-tracking systems. This is obtained by simply applying the areas of interest captured by the egocentric devices to standard, non-supervised image segmentation. We especially stress the importance in terms of time of using such eye-tracking devices on head-mounted systems to jointly perform image acquisition and automatic annotation. A gain of time of over 10-fold by comparison with classical image acquisition followed by manual image annotation is demonstrated.

Does 3D stereoscopy support anatomical education?

PURPOSE: The teaching of anatomy in medical education has historically been based on lectures, cadaveric dissections, and illustrated books for students. Stereoscopic 3D videos are now easily accessible via smartphone and affordable for students. This study aimed to investigate whether a 3D stereoscopic instruction video could improve learning over 2D video. METHODS: A prospective controlled study on a single-site was conducted at the University of Angers. Content knowledge was assessed, followed by the presentation of an instructional neuroanatomy video. Participants watched the video in either 3D or 2D format, then they completed an anatomy written test. Pre-video and post-video performances were analyzed with independent t tests on total score, fundamental anatomical knowledge, anatomical relationships and reasoning. RESULTS: 175 subjects completed the study. At baseline, the 3D (n = 91) and 2D (n = 86) groups were similar, in age and class level. 3D and 2D scores were similar in the pre-test session and in the fundamental knowledge post-test (mean 73.2% vs 74.4%, p = 0.37). Average scores for the 3D group were better for the post-test regarding anatomical relationships (mean 86.4% vs. 63.5%, p = 0.004), clinical inference/reasoning (mean 76.8% vs. 67.6%, p = 0.023) and total note (mean 76.8% vs. 67.6%, p = 0.07). Regarding the 3D student's satisfaction questionnaire (n = 91), 70 students (77%) agreed that the stereoscopic video allowed good 3D visualization of anatomical structures. The student enjoyed using the stereoscopic video (n = 75, 82.5%). Most students supported the use of this kind of stereoscopic 3D video in their normal teaching as a complementary tool (n = 78, 85%). CONCLUSIONS: The incorporation of 3D videos as ancillary teaching into curricula could be of interest to improve the knowledge of anatomical relationships and reasoning among students.

Acute decrease in plasma testosterone and appetite after either glucose or protein beverages in adolescent males.

OBJECTIVE: Chronic testosterone blood concentrations associate with food intake (FI), but acute effects of testosterone on appetite and effect of protein and glucose consumption on testosterone response have had little examination. METHODS: In a randomized, crossover study, twenty-three adolescent (12-18 years old) males were given beverages containing either: (a) whey protein (1 g/kg body weight), (b) glucose (1 g/kg body weight) or (c) a calorie-free control (C). Plasma testosterone, luteinizing hormone (LH), GLP-1 (active), ghrelin (acylated), glucose, insulin and subjective appetite were measured prior (0) and at 20, 35 and 65 minutes after the consumption of the beverage. FI at an ad libitum pizza meal was assessed at 85 minutes. RESULTS: Testosterone decreased acutely to 20 minutes after both protein and glucose with the decrease continuing after protein but not glucose to 65 minutes (P = 0.0382). LH was also decreased by both protein and glucose, but glucose had no effect at 20 minutes in contrast to protein (P < 0.001). Plasma testosterone concentration correlated positively with LH (r = 0.58762, P < 0.0001) and negatively with GLP-1 (r = -0.50656, P = 0.0003). No associations with appetite, ghrelin or glycaemic markers were found. Food intake was not affected by treatments. CONCLUSION: Protein or glucose ingestion results in acute decreases in both plasma testosterone and LH in adolescent males. The physiological significance of this response remains to be determined as no support for testosterone's role in acute regulation of food intake was found.

The Safety and Efficacy of Regional Citrate Anticoagulation in Albumin-Assisted Liver Dialysis for Extracorporeal Liver Support in Pediatric Patients.

AIMS: To establish the safety and efficacy of regional citrate anticoagulation (RCA) for pediatric liver failure (LF) patients receiving extracorporeal liver support (ELS) with albumin-assisted dialysis. METHODS: Retrospective review of pediatric LF patients receiving ELS from April 2014 to December 2016 at a tertiary children's hospital pediatric intensive care unit. Demographic and ELS data collected by chart review. Citrate accumulation (CA) was defined as total calcium (mmol/L): ionized calcium (mmol/L) > 2.5 (tCa:iCa). Efficacy was assessed by treatment duration. Safety was assessed by adverse events: bleeding, hemodynamic instability, arrhythmias, unplanned treatment discontinuation. RESULTS: Fifteen patients (median age 3 [interquartile range (IQR) 0.7-8.0]) received 108 ELS treatments (median 5 [IQR 4-7.5]). Sixty-eight episodes of CA were identified. Of those, 6 coincided with intervention and 1 coincided with ELS discontinuation. There were no deaths attributed to ELS or RCA. CONCLUSION: RCA provides safe and effective anticoagulation for pediatric LF patients requiring ELS.

The potential of virtual reality-based training to enhance the functional autonomy of Alzheimer's disease patients in cooking activities: A single case study.

Impairments in performing activities of daily living occur early in the course of Alzheimer's disease (AD). There is a great need to develop non-pharmacological therapeutic interventions likely to reduce dependency in everyday activities in AD patients. This study investigated whether it was possible to increase autonomy in these patients in cooking activities using interventions based on errorless learning, vanishing-cue, and virtual reality techniques. We recruited a 79-year-old woman who met NINCDS-ADRDA criteria for probable AD. She was trained in four cooking tasks for four days per task, one hour per day, in virtual and in real conditions. Outcome measures included subjective data concerning the therapeutic intervention and the experience of virtual reality, repeated assessments of training activities, neuropsychological scores, and self-esteem and quality of life measures. The results indicated that our patient could relearn some cooking activities using virtual reality techniques. Transfer to real life was also observed. Improvement of the task performance remained stable over time. This case report supports the value of a non-immersive virtual kitchen to help people with AD to relearn cooking activities.

Technical aspects of transcarotid artery revascularization using the ENROUTE transcarotid neuroprotection and stent system.

Transcarotid artery revascularization (TCAR) with the ENROUTE transcarotid neuroprotection and stent system (Silk Road Medical, Inc, Sunnyvale, Calif) combines surgical principles of neuroprotection with less invasive endovascular techniques to treat high grade stenosis in the carotid artery. The ENROUTE Neuroprotection System allows the surgeon to directly access the common carotid artery to initiate high rate temporary blood flow reversal to protect the brain while performing carotid angioplasty and stenting. Unprotected catheterization of the arch and lesion is, thus, avoided. Pivotal data from the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) study of high-risk patients undergoing TCAR have showed a low stroke rate compared with other prospective trials of endovascular carotid intervention. The aim of this article is to provide specific technical details of TCAR.

Tumour but not stromal expression of ß3 integrin is essential, and is required early, for spontaneous dissemination of bone-metastatic breast cancer.

Although many preclinical studies have implicated ß3 integrin receptors (αvß3 and αIIbß3) in cancer progression, ß3 inhibitors have shown only modest efficacy in patients with advanced solid tumours. The limited efficacy of ß3 inhibitors in patients could arise from our incomplete understanding of the precise function of ß3 integrin and, consequently, inappropriate clinical application. Data from animal studies are conflicting and indicate heterogeneity with respect to the relative contributions of ß3-expressing tumour and stromal cell populations in different cancers. Here we aimed to clarify the function and relative contributions to metastasis of tumour versus stromal ß3 integrin in clinically relevant models of spontaneous breast cancer metastasis, with particular emphasis on bone metastasis. We show that stable down-regulation of tumour ß3 integrin dramatically impairs spontaneous (but not experimental) metastasis to bone and lung without affecting primary tumour growth in the mammary gland. Unexpectedly, and in contrast to subcutaneous tumours, orthotopic tumour vascularity, growth and spontaneous metastasis were not altered in mice null for ß3 integrin. Tumour ß3 integrin promoted migration, protease expression and trans-endothelial migration in vitro and increased vascular dissemination in vivo, but was not necessary for bone colonization in experimental metastasis assays. We conclude that tumour, rather than stromal, ß3 expression is essential and is required early for efficient spontaneous breast cancer metastasis to bone and soft tissues. Accordingly, differential gene expression analysis in cohorts of breast cancer patients showed a strong association between high ß3 expression, early metastasis and shorter disease-free survival in patients with oestrogen receptor-negative tumours. We propose that ß3 inhibitors may be more efficacious if used in a neoadjuvant setting, rather than after metastases are established.

Detection of dengue virus in individual Aedes aegypti mosquitoes in Delhi, India.

BACKGROUND & OBJECTIVES: Delhi, the capital city of India, has so far witnessed several outbreaks of dengue fever since 1967 (last one reported in 2013). Improved virological and entomological surveillance are the only tools that can help in prevention of dengue as well as in the development of dengue control programmes. The aim of the study was to conduct a prospective field study to detect dengue virus in adult Aedes aegypti mosquitoes collected from various localities represented by different socioeconomic groups in Delhi. METHODS: The study areas were selected and categorized into high, medium and low income groups on the basis of socioeconomical characteristics of the resident population, where dengue cases were reported during the past three years by MCD. Dengue viral infection was detected in the head squash of each adult mosquito by immunofluorescent assay (IFA) employing monoclonal antibodies against dengue virus (DENV). A total of 2408 females and 1206 males of Ae. aegypti were collected and tested by IFA. RESULTS: Out of 2408 Ae. aegypti females, 14 were found positive, with minimum infection rate (MIR) of 5.8 per 1000 mosquitoes. Among the 18 study areas, 11 localities were found positive for dengue virus infection. Low income group (LIG) areas showed highest mosquito infectivity (9.8), followed by medium income group (MIG), i.e. 6.2; while least was observed in high income group (HIG), i.e. 1.3. No vertical transmission of dengue virus could be detected in 1206 Ae. aegypti males collected. INTERPRETATION & CONCLUSION: The study concludes that there was high MIR in the identified localities of low and medium income groups. Estimation of MIR in a female Aedes mosquito in the existing arsenals for dengue surveillance would be an added advantage for early warning of dengue outbreak. The presence of infected mosquitoes in identified localities of Delhi was alarming and require rigorous vector surveillance so that the severe outbreaks can be prevented.

Detecting everyday action deficits in Alzheimer's disease using a nonimmersive virtual reality kitchen.

Alzheimer's disease (AD) causes impairments affecting instrumental activities of daily living (IADL). Transdisciplinary research in neuropsychology and virtual reality has fostered the development of ecologically valid virtual tools for the assessment of IADL, using simulations of real life activities. Few studies have examined the benefits of this approach in AD patients. Our aim was to examine the utility of a non-immersive virtual coffee task (NI-VCT) for assessment of IADL in these patients. We focus on the assessment results obtained from a group of 24 AD patients on a task designed to assess their ability to prepare a virtual cup of coffee, using a virtual coffee machine. We compared performance on the virtual task to an identical daily living task involving the actual preparation of a cup of coffee, as well as to global cognitive, executive, and caregiver-reported IADL functioning. Relative to 32 comparable, healthy elderly (HE) controls, AD patients performed worse than HE controls on all tasks. Correlation analyses revealed that NI-VCT measures were related to all other neuropsychological measures. Moreover, regression analyses demonstrated that performance on the NI-VCT predicted actual task performance and caregiver-reported IADL functioning. Our results provide initial support for the utility of our virtual kitchen for assessment of IADL in AD patients.

Transient cyclical methylation of promoter DNA.

Methylation of CpG dinucleotides is generally associated with epigenetic silencing of transcription and is maintained through cellular division. Multiple CpG sequences are rare in mammalian genomes, but frequently occur at the transcriptional start site of active genes, with most clusters of CpGs being hypomethylated. We reported previously that the proximal region of the trefoil factor 1 (TFF1, also known as pS2) and oestrogen receptor alpha (ERalpha) promoters could be partially methylated by treatment with deacetylase inhibitors, suggesting the possibility of dynamic changes in DNA methylation. Here we show that cyclical methylation and demethylation of CpG dinucleotides, with a periodicity of around 100 min, is characteristic for five selected promoters, including the oestrogen (E2)-responsive pS2 gene, in human cells. When the pS2 gene is actively transcribed, DNA methylation occurs after the cyclical occupancy of ERalpha and RNA polymerase II (polII). Moreover, we report conditions that provoke methylation cycling of the pS2 promoter in cell lines in which pS2 expression is quiescent and the proximal promoter is methylated. This coincides with a low-level re-expression of ERalpha and of pS2 transcripts.

Potential of Synbiotics and Probiotics as Chemopreventive Agent.

Cancer remains a global problem, with millions of new cases diagnosed yearly and countless lives lost. The financial burden of cancer therapy, along with worries about the long-term safety of existing medicines, necessitates the investigation of alternative approaches to cancer prevention. Probiotics generate chemopreventive compounds such as bacteriocins, short-chain fatty acids (SCFA), and extracellular polymeric substances (EPS), which have demonstrated the ability to impede cancer cell proliferation, induce apoptosis, and bolster the expression of pro-apoptotic genes. On the other hand, prebiotics, classified as non-digestible food ingredients, promote the proliferation of probiotics within the colon, thereby ensuring sustained functionality of the gut microbiota. Consequently, the synergistic effect of combining prebiotics with probiotics, known as the synbiotic effect, in dietary interventions holds promise for potentially mitigating cancer risk and augmenting preventive measures. The utilization of gut microbiota in cancer treatment has shown promise in alleviating adverse health effects. This review explored the potential and the role of probiotics and synbiotics in enhancing health and contributing to cancer prevention efforts. In this review, the applications of functional probiotics and synbiotics, the mechanisms of action of probiotics in cancer, and the relationship of probiotics with various drugs were discussed, shedding light on the potential of probiotics and synbiotics to alleviate the burdens of cancer treatment.

Insecticide Resistance in Aedes aegypti from the National Capital Region of the Philippines.

Human arboviral diseases such as dengue, chikungunya, and Zika can be transmitted by the mosquito Aedes aegypti. The insecticide-based vector control strategy is critical in reducing transmission of these Aedes-borne diseases but is threatened mainly by the emergence of insecticide resistance. Adult Ae. aegypti from the National Capital Region (NCR), Philippines, were subjected to bioassays to determine their susceptibility to diagnostic doses of pyrethroid, organochlorine, and organophosphate insecticides following the standard World Health Organization insecticide susceptibility test. This study reports the detection of insecticide resistance to pyrethroids and organochlorine in Ae. aegypti from the Philippines for the first time. Most of the Ae. aegypti populations from NCR exhibited phenotypic resistance to permethrin, etofenprox, and DDT. Varying resistance levels to deltamethrin, cyfluthrin, and lambda-cyhalothrin were observed in the different mosquito populations, while all populations tested to malathion were susceptible to this organophosphate. This finding should alert public health authorities to consider modifying the existing vector management package for greater control efficacy. Best practices proven to prevent or delay the development of insecticide resistance, such as insecticide rotation, should also be implemented, while alternative chemicals with a different mode of action should be explored to ensure the continuing efficacy of program interventions.

Consensus on intake questionnaire data elements in the development of an aerodigestive registry.

OBJECTIVE: To define the essential elements of the intake questionnaire that will be a part of a larger multicenter registry for aerodigestive patients. METHODS: A modified Delphi method was utilized to obtain consensus on the data elements that should warrant inclusion in the final research database. Patient questionnaires from the eight participating institutions were reviewed and individual elements were aggregated into 14 categories. RESULTS: A total of 198 initial elements were voted on for inclusion. The categories included demographics, respiratory symptoms, gastrointestinal symptoms, ear nose and throat symptoms, feeding, birth history, medical history, surgical history, family history, social history, medications prior to evaluation, devices used prior to evaluation, prior diagnostic evaluations, and prior evaluation by aerodigestive team members. 83 of the 198 elements met consensus for inclusion in the final registry for an inclusion rate of 41.9 %. Three separate rounds of ranking were required to obtain consensus. CONCLUSION: The aerodigestive registry is an important initiative that will help foster research and help guide future management. The intake questionnaire of the registry is a critical component of this project, and the consensus obtained during this study should help create a streamlined and efficient registry that will help all aerodigestive patients on a national level.

Obstructive lung disease is common in children with syndromic and congenital scoliosis: a preliminary study.

BACKGROUND: It is well known that restrictive lung disease (RLD) is associated with scoliosis. This study identifies that obstructive lung disease (OLD) is associated with syndromic scoliosis and congenital scoliosis. METHODS: We searched a local database for patients with scoliosis who underwent a pulmonary function testing (PFT) from 2004 to 2009. All patients with congenital scoliosis or syndromic thoracolumbar scoliosis with a Cobb angle of ≥40 degrees and acceptable and repeatable PFT testing were included in the study. OLD was defined as an forced expiratory volume in the first second/forced vital capacity ratio below 95% confidence interval. Bronchoscopy videos and computed tomography scans or magnetic resonance images were reviewed to identify anatomic causes of lower airway disease. RESULTS: A total of 18 patients met the criteria for inclusion. The median age at diagnosis was 11.3 years. The median primary Cobb angle was 60 degrees. The prevalence of OLD was 33% and RLD was 57%. The 6 children with OLD underwent preoperative bronchoscopy and chest computed tomography or magnetic resonance imaging to identify anatomic causes of lower airway obstruction. The 4 children with OLD and right-sided major thoracic curves had compression of the right mainstem bronchus between the spine (posterior) and the right pulmonary artery (anterior). The 2 children with OLD and left-sided major thoracic curves had compression of the left mainstem bronchus between the spine (posterior) and the descending aorta (anterior) or the left atrium (anterior). CONCLUSIONS: In our study, the prevalence of OLD in children with congenital scoliosis or syndromic scoliosis was 33%, which was elevated when compared with the population prevalence of 2% to 5%. Mainstem airway compression from spine rotation was discovered to be the potential mechanism of disease. LEVEL OF EVIDENCE: Level IV, prognostic study investigating the effect of a patient characteristic on the outcome of disease.

Predictive power of chest radiography for infectious or inflammatory lung disease.

OBJECTIVE: Children frequently present with chronic cough, recurrent respiratory infections, and dysphagia. These symptoms are poor predictors of significant inflammatory lung disease, such as from chronic aspiration. Bronchoalveolar lavage (BAL) is the gold standard for identification of lung infection and airway inflammation but is expensive and requires sedation. Chest X-rays (CXR) are inexpensive, low-radiation tests that do not require sedations and can document findings associated with infectious or inflammatory lung disease. The accuracy of CXR to predict or exclude infectious or inflammatory lung disease has not been directly evaluated and is unknown. METHODS: Retrospective cohort of all pediatric patients who underwent FFB with BAL within 2 weeks of a CXR. Blinded CXR images reviewed for findings consistent with inflammatory disease by two senior pediatric radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CXR to identify significant inflammation and/or infection on BAL were calculated. RESULTS: Three hundred and forty-four subjects included. Two hundred and sixty-three had positive CXR (77%), 183 had inflammatory BAL (53%), and 110 had infection (32%). The sensitivity of CXR changes for BAL inflammation, infection, and either inflammation or infection was 84.7, 90.9, and 85.3, respectively. The PPV of CXR was 58.9, 38.0, and 59.7. The NPV of CXR was 65.0, 87.5, and 66.3. CONCLUSIONS: Although CXR are inexpensive, do not require sedation, and are of low radiation dose, the ability of an entirely normal CXR to exclude active inflammatory or infectious lung disease is limited.

Expert consensus recommendations for the provision of infective endocarditis services: updated guidance from the Joint British Societies.

Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.

Systematic review of the incidence and clinical risk predictors of atrial fibrillation and permanent pacemaker implantation for bradycardia in Fabry disease.

INTRODUCTION: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by enzyme deficiency, leading to glycosphingolipid accumulation. Cardiac accumulation triggers local tissue injury, electrical instability and arrhythmia. Bradyarrhythmia and atrial fibrillation (AF) incidence are reported in up to 16% and 13%, respectively. OBJECTIVE: We conducted a systematic review evaluating AF burden and bradycardia requiring permanent pacemaker (PPM) implantation and report any predictive risk factors identified. METHODS: We conducted a literature search on studies in adults with FD published from inception to July 2019. Study outcomes included AF or bradycardia requiring therapy. Databases included Embase, Medline, PubMed, Web of Science, CINAHL and Cochrane. The Risk of Bias Agreement tool for Non-Randomised Studies (RoBANS) was utilised to assess bias across key areas. RESULTS: 11 studies were included, eight providing data on AF incidence or PPM implantation. Weighted estimate of event rates for AF were 12.2% and 10% for PPM. Age was associated with AF (OR 1.05-1.20 per 1-year increase in age) and a risk factor for PPM implantation (composite OR 1.03). Left ventricular hypertrophy (LVH) was associated with AF and PPM implantation. CONCLUSION: Evidence supporting AF and bradycardia requiring pacemaker implantation is limited to single-centre studies. Incidence is variable and choice of diagnostic modality plays a role in detection rate. Predictors for AF (age, LVH and atrial dilatation) and PPM (age, LVH and PR/QRS interval) were identified but strength of association was low. Incidence of AF and PPM implantation in FD are variably reported with arrhythmia burden likely much higher than previously thought. PROSPERO DATABASE: CRD42019132045.