Risk of atrial fibrillation in athletes: a systematic review and meta-analysis

Objective A systematic review, meta-analysis and meta-regression were performed on selected studies to investigate the incidence of atrial fibrillation (AF) among athletes compared with non-athlete controls. Design Meta-analysis with heterogeneity analysis and subsequent meta-regression to model covariates were performed. The mode of exercise (endurance and mixed sports) and age were the a priori determined covariates. Data sources PubMed, MEDLINE, Science Direct, SPORTDiscus and the Cochrane library were searched. Eligibility criteria Research articles published after 1990 and before 2 December 2020 were included if they reported the number of AF cases in athletes with non-athlete (physically active or inactive) control groups, were case–control or cohort studies and if data allowed calculation of OR. Results The risk of developing AF was significantly higher in athletes than in non-athlete controls (OR: 2.46; 95% CI 1.73 to 3.51; p<0.001, Z=4.97). Mode of exercise and risk of AF were moderately correlated (B=0.1259, p=0.0193), with mixed sport conferring a greater risk of AF than endurance sport (B=−0.5476, p=0.0204). Younger (<55 years) athletes were significantly more likely to develop AF compared with older (≥55 years) athletes (B=−0.02293, p<0.001). Conclusion Athletes have a significantly greater likelihood of developing AF compared with non-athlete controls, with those participating in mixed sport and younger athletes at the greatest risk. Future studies of AF prevalence in athletes according to specific exercise dose parameters, including training and competition history, may aid further in delineating those at risk

Use of probiotics in preventing antibiotic associated diarrhoea and Clostridium difficile associated diarrhoea in spinal injury centres: An international survey of four western European countries

Probiotics may prevent antibiotic-associatedand Clostridium difficile-associated- diarrhoea (AAD/CDAD). Many spinal cord injury centres (SCICs) practitioners consider probiotics generically and may not realise that efficacy can be strain-, dose-, and disease-specific. One to four SCICs per country (depending on population size) were contacted (UK:4; the Netherlands:3; Belgium: I; Republic of Ireland: 1) to (a) determine if they stocked probiotics; (b) determine whether the use of those probiotics was evidence-based; and (c) document their C. difficile infection (CDI) practices. All nine SCICs responded to the survey (7 physicians, 3 microbiologists, 1 nurse and 2 dietitians). Five (55.5%) stocked probiotics; five different probiotics were identified. Four probiotics were preferred choice prevention o f AAD/CDAD were Lactobacillus casei Shirota (44.4%), L. casei D N -114001 (22.2%), L. acidophilus (22.2%) and a mixed-strains probiotic (Ecologic Pro-AD) (11.1%). Only one evidence base study was identified supporting the use of probiotic for prevention of AAD in SCI patients. Mean CDI cases per 10,000 patient-days were 0.307 (s.d: 0.486, range 0.00 to 1.08). Definitions of diarrhoea and CDI varied among SCICs. Stocking probiotics for the prevention of AAD / CDAD is not common. There is only one single study showing efficiency of a particular strain in SCI populations. The study highlighted the importance of using a standardised definition o f diarrhoea when conducting AAD/CDAD research

Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome

A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression

Controlled release strategies for bone, cartilage, and osteochondral engineering: part I: recapitulation of native tissue healing and variables for the design of delivery systems

The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriersfor controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules.The authors thank Fundacao para a Ciencia e Tecnologia for V.E.Santo's PhD grant (SFRH/BD/39486/2007). This work was carried out under the scope of the European FP7 Project Find and Bind (NMP4-SL-2009-229292) and Project MIT/ECE/0047/2009

Real-world performance and accuracy of stress echocardiography: The EVAREST observational multi-centre study

Aims - Stress echocardiography is widely used to identify obstructive coronary artery disease. High accuracy is reported in expert hands but is dependent on operator training and image quality. The EVAREST study provides UK-wide data to evaluate real-world performance and accuracy of stress echocardiography. Methods and Results - Participants undergoing stress echocardiography for coronary artery disease were recruited from 31 hospitals. Participants were followed up through health records which underwent expert adjudication. Cardiac outcome was defined as anatomically or functionally-significant stenosis on angiography, revascularisation, medical management of ischaemia, acute coronary syndrome or cardiac-related death within six months. 5131 patients (55% male) participated with a median age of 65 years (IQR 57 – 74). 72.9% of studies used dobutamine and 68.5% were contrast studies. Inducible ischaemia was present in 19.3% of scans. Sensitivity and specificity for prediction of a cardiac outcome were 95.4% and 96.0%, respectively, with an accuracy of 95.9%. Sub-group analysis revealed high levels of predictive accuracy across a wide range of patient and protocol sub-groups, with the presence of a resting regional wall motion abnormalitiy significantly reducing the performance of both dobutamine (p<0.01) and exercise (p<0.05) stress echocardiography (p<0.05). Overall accuracy remained consistently high across all participating hospitals. Conclusion – Stress echocardiography has high accuracy across UK-based hospitals and thus indicates stress echocardiography is being delivered effectively in real-world practice, reinforcing its role as a first-line investigation in the assessment of patients with stable chest pain

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Itraconazole associated quadriparesis and edema: a case report

<p>Abstract</p> <p>Introduction</p> <p>Itraconazole is an anti-fungal agent widely used to treat various forms of mycosis. It is particularly useful in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Side effects are uncommon and usually mild. Mild neuropathy is noted to occur very rarely. We present an unusual and, to the best of our knowledge, as yet unreported case of severe neuropathy and peripheral edema due to itraconazole in the absence of a concomitant risk factor.</p> <p>Case presentation</p> <p>A 72-year-old Caucasian man was started on itraconazole following diagnosis of severe asthma with fungal sensitization. One month later he presented with severe bilateral ankle edema with an elevated serum itraconazole level. The itraconazole dose was reduced but his ankle edema persisted and he developed weakness of all four limbs. Itraconazole was completely stopped leading to improvement in his leg edema but he became bed bound due to weakness. He gradually improved with supportive care and neurorehabilitation. On review at six months, our patient was able to mobilize with the aid of two elbow crutches and power had returned to 5/5 in distal extremities and 4+/5 in proximal extremities. The diagnosis was established based on the classical presentation of drug-induced neuropathy and negative investigatory findings for any alternative diagnoses.</p> <p>Conclusion</p> <p>We report the case of a patient presenting with an unusual complication of severe neuropathy and peripheral edema due to itraconazole. Clinicians should be alert to this association when encountered with neuropathy and/or edema in an itraconazole therapy recipient.</p

Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis

BACKGROUND: Malignant melanoma, generally described as incurable, is notoriously refractory to chemotherapy. The mechanisms contributing to this have not yet been defined and the contributions of drug efflux pumps, implicated in chemo-resistance of many other cancer types, have not been extensively investigated in melanoma. METHODS: In this study, expression of multi-drug resistant (MDR1/P-gp and MRP-1) proteins was examined, by immunohistochemistry, in archival specimens from 134 melanoma patients. This included 92 primary tumours and 42 metastases. RESULTS: On assessing all specimens, MRP-1 and MDR1/P-gp expression was found to be common, with the majority (81%) of melanomas expressing at least one of these efflux pumps. Although there is significant association between expression of these pumps (P=0.007), MRP-1 was found to be the predominant (67% of cases) form detected. chi(2) analysis showed significant associations between expression of MRP-1 and/or MDR1/P-gp and the aggressive nature of this disease specifically increased Breslow's depth, Clark's level and spread to lymph nodes. This association with aggressiveness and spread is further supported by the observation that a significantly higher percentage of metastases, than primary tumours, express MRP-1 (91% vs 57%; P<0.0001) and MDR1/P-gp (74% vs 50%; P=0.010). CONCLUSION: The predominant expression of these pumps and, in particular, MRP-1 suggests that they may be important contributors to the inherent aggressive and resistant nature of malignant melanoma

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline