Recent Submissions

  • Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative.

    Giorgi Rossi, Paolo; Lebeau, Annette; Canelo-Aybar, Carlos; Saz-Parkinson, Zuleika; Quinn, Cecily; Langendam, Miranda; McGarrigle, Helen; Warman, Sue; Rigau, David; Alonso-Coello, Pablo; et al. (2021-02-18)
    Background: Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question "Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?" Methods: The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS). Results: Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests. Conclusions: The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).
  • Vitamin D and Hospital Admission in Older Adults: A Prospective Association.

    Beirne, Avril; McCarroll, Kevin; Walsh, James Bernard; Casey, Miriam; Laird, Eamon; McNulty, Helene; Ward, Mary; Hoey, Leane; Molloy, Anne M; Healy, Martin; et al. (2021-02-14)
    The health effects of vitamin D are well documented, with increasing evidence of its roles beyond bone. There is, however, little evidence of the effects of vitamin D on hospitalisation among older adults. This study aimed to prospectively determine the relationship of vitamin D status in older adults with hospital admission and emergency department (ED) attendance. Trinity University of Ulster Department of Agriculture (TUDA) is a large cross-sectional study of older adults with a community population from three disease-defined cohorts (cognitive dysfunction, hypertension, and osteoporosis). Participants included in this analysis were recruited between 2008 and 2012. ED and hospital admission data were gathered from the date of TUDA participation until June 2013, with a mean follow up of 3.6 years. Of the 3093 participants, 1577 (50.9%) attended the ED during the period of follow-up. Attendees had lower mean serum 25(OH)D concentrations than non-attendees (59.1 vs. 70.6 nmol/L). Fully adjusted models showed an inverse association between vitamin D and ED attendance (Hazard Ratio (HR) 0.996; 95% Confidence Interval (CI) 0.995-0.998; p < 0.001). A total of 1269 participants (41%) were admitted to hospital during the follow-up. Those admitted had lower mean vitamin D concentrations (58.4 vs. 69.3 nmol/L, p < 0.001). In fully adjusted models, higher vitamin D was inversely associated with hospital admission (HR 0.996; 95% CI 0.994-0.998; p < 0.001) and length of stay (LOS) (β = -0.95, p = 0.006). This study showed independent prospective associations between vitamin D deficiency and increased hospitalisation by older adults. The need for further evaluation of current recommendations in relation to vitamin D supplementation, with consideration beyond bone health, is warranted and should focus on randomised controlled trials.
  • Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain.

    Rodríguez, Alejandro; Ruiz-Botella, Manuel; Martín-Loeches, Ignacio; Jimenez Herrera, María; Solé-Violan, Jordi; Gómez, Josep; Bodí, María; Trefler, Sandra; Papiol, Elisabeth; Díaz, Emili; et al. (2021-02-15)
    Background The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. Methods Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient’s factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. Results The database included a total of 2022 patients (mean age 64 [IQR 5–71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10–17]) and SOFA score (5 [IQR 3–7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. Conclusion The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a “one-size-fits-all” model in practice.
  • Outcomes in Antiplatelet-Associated Intracerebral Hemorrhage in the TICH-2 Randomized Controlled Trial.

    Law, Zhe Kang; Desborough, Michael; Roberts, Ian; Al-Shahi Salman, Rustam; England, Timothy J; Werring, David J; Robinson, Thompson; Krishnan, Kailash; Dineen, Robert; Laska, Ann Charlotte; et al. (2021-02-15)
    Abstract Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use.
  • The Role of Organoids as a Novel Platform for Modeling of Inflammatory Bowel Disease.

    O'Connell, Lauren; Winter, Des C; Aherne, Carol M (2021-02-17)
    Inflammatory bowel disease (IBD) is a chronic relapsing-remitting immune-mediated disorder affecting the gut. It is common in Westernized regions and is increasing in incidence in developing countries. At a molecular level, intrinsic deficiencies in epithelial integrity, mucosal barrier function, and mechanisms of immune response and resolution contribute to the development of IBD. Traditionally two platforms have been utilized for disease modeling of IBD; in-vitro monolayer cell culture and in-vivo animal models. Both models have limitations, including cost, lack of representative cell types, lack of complexity of cellular interactions in a living organism, and xenogeneity. Organoids, three-dimensional cellular structures which recapitulate the basic architecture and functional processes of the organ of origin, hold potential as a third platform with which to investigate the pathogenesis and molecular defects which give rise to IBD. Organoids retain the genetic and transcriptomic profile of the tissue of origin over time and unlike monolayer cell culture can be induced to differentiate into most adult intestinal cell types. They may be used to model intestinal host-microbe interactions occurring at the mucosal barrier, are amenable to genetic manipulation and can be co-cultured with other cell lines of interest. Bioengineering approaches may be applied to render a more faithful representation of the intestinal epithelial niche. In this review, we outline the concept of intestinal organoids, discuss the advantages and disadvantages of the platform comparative to alternative models, and describe the translational applications of organoids in IBD.
  • Distance Management of Spinal Disorders During the COVID-19 Pandemic and Beyond: Evidence-Based Patient and Clinician Guides From the Global Spine Care Initiative.

    Haldeman, Scott; Nordin, Margareta; Tavares, Patricia; Mullerpatan, Rajani; Kopansky-Giles, Deborah; Setlhare, Vincent; Chou, Roger; Hurwitz, Eric; Treanor, Caroline; Hartvigsen, Jan; et al. (2021-02-17)
    Abstract: Background The COVID-19 pandemic has greatly limited patients' access to care for spine-related symptoms and disorders. However, physical distancing between clinicians and patients with spine-related symptoms is not solely limited to restrictions imposed by pandemic-related lockdowns. In most low- and middle-income countries, as well as many underserved marginalized communities in high-income countries, there is little to no access to clinicians trained in evidence-based care for people experiencing spinal pain. Objective The aim of this study is to describe the development and present the components of evidence-based patient and clinician guides for the management of spinal disorders where in-person care is not available. Methods Ultimately, two sets of guides were developed (one for patients and one for clinicians) by extracting information from the published Global Spine Care Initiative (GSCI) papers. An international, interprofessional team of 29 participants from 10 countries on 4 continents participated. The team included practitioners in family medicine, neurology, physiatry, rheumatology, psychology, chiropractic, physical therapy, and yoga, as well as epidemiologists, research methodologists, and laypeople. The participants were invited to review, edit, and comment on the guides in an open iterative consensus process. Results The Patient Guide is a simple 2-step process. The first step describes the nature of the symptoms or concerns. The second step provides information that a patient can use when considering self-care, determining whether to contact a clinician, or considering seeking emergency care. The Clinician Guide is a 5-step process: (1) Obtain and document patient demographics, location of primary clinical symptoms, and psychosocial information. (2) Review the symptoms noted in the patient guide. (3) Determine the GSCI classification of the patient’s spine-related complaints. (4) Ask additional questions to determine the GSCI subclassification of the symptom pattern. (5) Consider appropriate treatment interventions. Conclusions The Patient and Clinician Guides are designed to be sufficiently clear to be useful to all patients and clinicians, irrespective of their location, education, professional qualifications, and experience. However, they are comprehensive enough to provide guidance on the management of all spine-related symptoms or disorders, including triage for serious and specific diseases. They are consistent with widely accepted evidence-based clinical practice guidelines. They also allow for adequate documentation and medical record keeping. These guides should be of value during periods of government-mandated physical or social distancing due to infectious diseases, such as during the COVID-19 pandemic. They should also be of value in underserved communities in high-, middle-, and low-income countries where there is a dearth of accessible trained spine care clinicians. These guides have the potential to reduce the overutilization of unnecessary and expensive interventions while empowering patients to self-manage uncomplicated spinal pain with the assistance of their clinician, either through direct in-person consultation or via telehealth communication.
  • Solitary Plasmacytoma Management and Outcomes

    Comerford, C; McKey, S; Wallace, N; McArdle, O; Faul, C; Glavey, S; Sargent, J; Thornton, P; Murphy, P T; Quinn, J (2019-06-17)
    Solitary plasmacytoma (SP) is a rare malignant tumour characterised by a localised collection of neoplastic plasma cells. SP is closely related to multiple myeloma (MM) which, in contrast, is characterised by widespread plasma cell neoplasia with systemic features including hypercalcaemia, bone disease, anaemia and/or renal impairment. SPs can manifest as a solitary bone plasmacytoma (SBP) or less commonly as a soft tissue mass i.e. solitary extramedullary plasmacytoma (SEP). SP is far less common than MM (~5% of plasma cell malignancies) and therefore there is a lack of high-quality data guiding management1. Like MM, SP is more common in males but has a lower median age of onset. SBP most commonly affects the axial skeleton 1,2, particularly the vertebrae, with SBP accounting for ~30% of malignant spinal bone tumours1. Less common sites of SBP include the ribs, clavicle and scapulae2. SEP (ratio approximately 10:1) are much less common than SBP1,3 and are most frequently seen in the upper respiratory tract and less commonly in the lower respiratory tract, gastrointestinal tract and rarely in sites such as breast and pituitary gland3. Five year overall survival(OS) following a diagnosis of SP is variable with reported ranges of 40-85%4.
  • Interferon lambda rs368234815 ΔG/ΔG is associated with higher CD4:CD8 T-cell ratio in treated HIV-1 infection.

    Freitas, Inês T; Tinago, Willard; Sawa, Hirofumi; McAndrews, Julie; Doak, Brenda; Prior-Fuller, Charlotte; Sheehan, Gerard; Lambert, John S; Muldoon, Eavan; Cotter, Aoife G; et al. (2020-04-15)
    Background: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. Methods: A cross-sectional study in PLWH enrolled into the Mater Immunology study. We performed IFNL genotyping on stored samples and evaluated the association of IFNL single-nucleotide polymorphisms (rs368234815 and rs12979860) with CD4+:CD8+ ratio normalization (> 1) and expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+ (central-memory), CD45RO+ CD62L-(effector-memory) and CD45RO-CD62L+ (naïve), using logistic and linear regression models, respectively. Results: 190 ambulatory PLWH recruited to the main study, 143 were included in the analysis (38 had no stored DNA and 9 no T-lymphocyte subpopulation). Of 143 included, the median age (IQR) was 45(39-48) years, 64% were male and 66% were of Caucasian ethnicity. Heterosexual-contact (36%), injecting drug-use (33%) and men who have sex with men (24%) were the most presented HIV-transmission risk groups. The majority of subjects (90.2%) were on ART with 79% of the cohort having an undetectable HIV-RNA (< 40 copies/ml) and the time since ART initiation was 7.5 (3.7-10.4) year. rs368234815 and rs12979860 displayed similar allelic frequencies, with minor alleles ΔG and T representing 39% and 42%, respectively, of circulating alleles. rs368234815 ΔG/ΔG minor homozygotes were significantly associated with increased odds for attaining a normalised CD4+:CD8+ ratio compared to rs368234815 T/T major homozygotes in PLWH virologically suppressed on effective ART (OR = 3.11; 95% CI [1.01:9.56]). rs368234815 ΔG/ΔG homozygosity was also significantly associated with lower levels of CD4+ effector memory T-cells (regression coefficient: - 7.1%, p = 0.04) and CD8+ naïve T-cell subsets were significantly higher in HIV-1 mono-infected PLWH with rs368234815 ΔG/ΔG (regression coefficient: + 7.2%, p = 0.04). Conclusions: In virally-suppressed, long-term ART-treated PLWH, rs368234815 ΔG/ΔG homozygotes were more likely to have attained normalisation of their CD4+:CD8+ ratio, displayed lower CD4+ effector memory and higher naive CD8+ T-cells. Further studies are needed to replicate our findings in other, larger and more diverse cohorts and to determine the impact of IFNL genetic-variation on CD4+:CD8+ ratio normalisation and clinical outcomes in PLWH. Keywords: CD4+; CD8+; HIV; Interferon lambda; T-cells.
  • CSF Rhinorrhea After Endonasal Intervention to the Skull Base (CRANIAL) - Part 2: Impact of COVID-19.

    CRANIAL Consortium (World Neurosurg ., 2021-01-11)
    Abstract Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised regarding the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, especially during endonasal neurosurgical operations. The Pituitary Society has produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the effects of COVID-19.
  • Reply to Blot and to Inoue

    McElvaney, Oliver J; McEvoy, Natalie L; McElvaney, Noel G; Curley, Gerard F; Royal College of Surgeons in Ireland Dublin, Ireland and. Beaumont Hospital Dublin, Ireland. (the American Thoracic Society, 2021-09-21)
    Reply to Blot et al. and to Inoue et al. From the Authors: We thank Blot and colleagues for their interest in our article and for raising an important question regarding the suitability of IL-6 as a therapeutic target in coronavirus disease (COVID-19). In their correspondence, Blot and colleagues provide data on IL-6 levels measured in patients with a diagnosis of COVID-19 versus non–COVID-19 pneumonia. Although we believe the data presented by Blot and colleagues are valid, we suggest that the IL-6 levels depicted are, by virtue of sample timing, processing methodology, and patient severity of disease, not comparable to ours and should be interpreted in context.
  • P084 The impact of the SARS-CoV-2 pandemic on people living with cystic fibrosis in Ireland: real-world data from the Irish cystic fibrosis registry

    Rees, H.; Babu, S.; Fletcher, G.; Kirwan, L. (Journal of Cystic Fibrosis, 2021-06-11)
    The impact of the SARS-CoV-2 pandemic on people living with cystic fibrosis (PWCF) in Ireland was investigated by comparing the utilisation of regular hospital facilities in 2020, with data collected in 2019.
  • Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland.

    McCabe, John Joseph; Giannotti, Nicola; McNulty, Jonathan; Collins, Sean; Coveney, Sarah; Murphy, Sean; Barry, Mary; Harbison, Joseph; Cronin, Simon; Williams, David; et al. (2020-07-19)
    Purpose: Inflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke. Participants: The Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%-99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts. Findings to date: We have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date. Future plans: The primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic 'culprit' carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events. Keywords: adult neurology; cardiovascular imaging; preventive medicine; stroke.
  • Competing mortality risks: predicted cardiovascular disease risk versus predicted risk of breast cancer mortality in patients receiving adjuvant chemotherapy in a single Irish center.

    Prior, Lisa; Featherstone, Hannah; O'Reilly, David; Nugent, Killian; Lim, Marvin; McCaffrey, John; Higgins, Michaela J; Kelly, Catherine M (2021-02-23)
    Background: Due to advances in care, most women diagnosed with breast cancer do not die from the disease itself. Instead, cardiovascular disease (CVD) remains the most frequent cause of death. Many breast cancer patients are older and have established CVD risk factors. They are at further risk due to exposure to anthracyclines, HER2 targeted agents, endocrine therapy and radiotherapy. In this study, we compared the 10-year predicted risk of breast cancer mortality versus that of cardiovascular (CV) morbidity/mortality in breast cancer patients receiving adjuvant chemotherapy using online predictive risk calculators. Furthermore, we evaluated the predicted outcome of CV risk factor optimisation on their overall CV risk. Methods: This was a cross sectional study. All patients with resected Stage I-III breast cancer who received adjuvant chemotherapy at our centre from September 2015 to November 2016 were identified. Data recorded included demographics, tumor characteristics, treatments and CV risk factors. To calculate predicted 10-year risk of CVD and impact of lifestyle changes, we used the JBS3 (Joint British Society) online risk calculator. To calculate the predicted 10-year risk of breast cancer mortality, we used the PREDICT calculator. Biostatistical methods included Wilcoxon signed rank test for predicted CVD risk pre and post cardiovascular risk optimization. Results: We identified 102 patients. Of this cohort, 76 patients were ≥ 50 years & 26 were < 50 years of age. The group had significant baseline cardiovascular risk factors: increased BMI (68 %, n = 70), ex-smoking (34 %, n = 35), current smoking (13 %, n = 13), hypertension (47 %, n = 47) and dyslipidemia (57 %). Of the total group, 48 % had a high (> 20 %) and 37 % had a moderate (10-20 %) 10-year predicted breast cancer mortality risk. Regarding 10-year predicted risk of CVD, 11 % and 22 % fell into the high (> 20 %) and moderate (10-20 %) risk categories, respectively. Assuming CV risk factor optimisation, there was a predicted improvement in median 10-year CV risk from 26.5 to 9.9 % (p = .005) in the high CVD risk group and from 14.0 to 6.6 % (p < .001) in the moderate CVD risk group. Conclusions: Benefits predicted with a CVD risk intervention model indicates that this should be incorporated into routine breast oncology care.
  • Association of artificial turf and concussion in competitive contact sports: a systematic review and meta-analysis.

    O' Leary, Frank; Acampora, Nic; Hand, Fiona; O' Donovan, James (2020-05-26)
    Objective: To determine the incidence of head injuries and concussion in contact sports, comparing natural grass with artificial turf surfaces. Design: Systematic review and meta-analysis via the RevMan V.5.3 software. Eligibility criteria for selecting studies: All studies describing competitive contact sports played on both natural grass and artificial turf. The primary outcome measured was occurrence of head injury and concussion. Data sources: The databases include PubMed, Embase, Cochrane, Medline and Sport Discus. The last search took place on 23 May 2019. The Newcastle-Ottawa Quality Assessment Scale evaluated the methodological quality of the selected studies with a funnel plot designed to determine publication bias. Study screening and data extraction were performed by two independent reviewers. Results: Initial screening generated 42 publications, with 12 meeting criteria for inclusion. Eight studies described concussion only. The rate ratio (RR) of head injury and concussion was less on artificial turf compared with natural grass (RR=0.89, 95% CI 0.77 to 1.04) as was the rate ratio of concussion only (RR=0.72, 95% CI 0.58 to 0.89). Conclusion: Analysis of published data demonstrates a decreased incidence of head injury and concussion when contact sports are played on artificial turf. This difference was most marked for sports such as rugby and American football. However, artificial turf has no association with the incidence of head injury or concussion while playing soccer. Keywords: concussion; contact sports; environment; head; injuries.
  • A model for occupational stress amongst paediatric and adult critical care staff during COVID-19 pandemic.

    Feeley, T; Ffrench-O'Carroll, R; Tan, M H; Magner, C; L'Estrange, K; O'Rathallaigh, E; Whelan, S; Lyons, B; O'Connor, E (2021-02-25)
    Purpose: The coronavirus 2019 pandemic has placed all intensive care unit (ICU) staff at increased risk of psychological distress. To date, measurement of this distress has largely been by means of validated assessment tools. We believe that qualitative data may provide a richer view of staff experiences during this pandemic. Methods: We conducted a cross-sectional, observational study using online and written questionnaires to all ICU staff which consisted of validated tools to measure psychological distress (quantitative findings) and open-ended questions with free-text boxes (qualitative findings). Here, we report our qualitative findings. We asked four questions to explore causes of stress, need for supports and barriers to accessing supports. A conventional content analysis was undertaken. Results: In total, 269 of the 408 respondents (65.9%) gave at least one response to a free-text question. Seven overarching themes were found, which contribute to our proposed model for occupational stress amongst critical care staff. The work environment played an important role in influencing the perceived psychological impact on healthcare workers. Extra-organisational factors, which we termed the "home-work interface" and uncertainty about the future, manifested as anticipatory anxiety, had a proportionally larger influence on worker well-being than would be expected in non-pandemic conditions. Conclusion: Our findings have important implications for appropriate allocation of resources and ensuring well-being of the ICU multidisciplinary team for this and future pandemics. Keywords: Anticipatory anxiety; COVID-19; Critical care staff; Home-work interface; Occupational stress; Pandemic; Work intensification.
  • Current concepts and outcomes in cemented femoral stem design and cementation techniques: the argument for a new classification system.

    Cassar-Gheiti, Adrian J; McColgan, Rosie; Kelly, Martin; Cassar-Gheiti, Theresa M; Kenny, Paddy; Murphy, Colin G (2020-04-02)
    Cemented implant fixation design principles have evolved since the 1950s, and various femoral stem designs are currently in use to provide a stable construct between the implant-cement and cement-bone interfaces. Cemented stems have classically been classified into two broad categories: taper slip or force closed, and composite beams or shaped closed designs. While these simplifications are acceptable general categories, there are other important surgical details that need to be taken into consideration such as different broaching techniques, cementing techniques and mantle thickness. With the evolution of cemented implants, the introduction of newer implants which have hybrid properties, and the use of different broaching techniques, the classification of a very heterogenous group of implants into simple binary categories becomes increasingly difficult. A more comprehensive classification system would aid in comparison of results and better understanding of the implants' biomechanics. We review these differing stem designs, their respective cementing techniques and geometries. We then propose a simple four-part classification system and summarize the long-term outcomes and international registry data for each respective type of cemented prosthesis. Cite this article: EFORT Open Rev 2020;5:241-252. DOI: 10.1302/2058-5241.5.190034.
  • Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome.

    Forde, Karina; Resta, Nicoletta; Ranieri, Carlotta; Rea, David; Kubassova, Olga; Hinton, Mark; Andrews, Katrina A; Semple, Robert; Irvine, Alan D; Dvorakova, Veronika (2021-02-27)
    Background: PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting in abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) is a novel, orally available, selective pan-AKT inhibitor with proven in vitro efficacy. Following recent results of the use of AKT inhibitors in Proteus syndrome (PS) and AKT-mutant cancers, we investigated its therapeutic use in two patients with severe PROS who had exhausted conventional treatment methods. Results: Two patients, one with CLOVES variant (P1) and one with facial infiltrating lipomatosis and hemimegalencephaly (P2), were commenced on miransertib treatment on a compassionate use basis. In patient one, intra-abdominal and paraspinal overgrowth had resulted in respiratory compromise, obstructive uropathy, dysfunctional seating and lying postures, and chronic pain. In patient two, hemifacial overgrowth and hemimegalencephaly had caused difficulties with articulation and oral function, and refractory epilepsy. Miransertib treatment was continued for a median duration of 22 months (range 22-28). In patient one, alleviation of respiratory compromise was observed and functionally, seating and lying postures improved. Serial volumetric MRI analysis revealed 15% reduction in calculated volumes of fatty overgrowth between treatment commencement and end. In patient two, reduction in seizure burden and improved parent-reported quality of life measures were reported. Treatment was discontinued in both patients due to lack of sustained response, and poor compliance in year two of treatment (P2). No significant toxicities were reported. Conclusion: We report the first paediatric case series of the use of miransertib in two children with PROS. Objective clinical response was observed in patient one, and improvement in key qualitative outcomes was reported in patient two. Treatment was well tolerated with no significant toxicities reported. This case series highlights the potential therapeutic utility of miransertib in selected paediatric patients with severe PROS, and further demonstrates the potential for re-purposing targeted therapies for the treatment of rare diseases. An open label, Phase 1/2 study of miransertib in children with PROS and PS is underway to more accurately assess the efficacy of miransertib in the treatment of PROS disorder (NCT03094832).
  • Rare chromosomal abnormalities: Can they be identified using conventional first trimester combined screening methods?

    Kane, Daniel; D'Alton, Mary E; Malone, Fergal D (2021-02-27)
    Objective: To evaluate the performance of first trimester combined screening for the detection of rare chromosomal abnormalities, other than Trisomies 21, 18 or 13 or 45 × . Study design: A database containing 36,254 pregnancies was analyzed. These patients were recruited at 15 US centers and included singleton pregnancies from 10 3/7-13 6/7 weeks. All patients had a nuchal translucency (NT) scan and those without a cystic hygroma (N = 36,120) underwent a combined first trimester screening test ('FTS' - NT, PAPP-A and fbHCG). A risk cut-off of 1:300, which was used for defining high risk for Trisomy 21, was also used to evaluate the detection rate for rare chromosomal abnormalities using the combined FTS test. Results: 36,120 patients underwent combined FTS. Of these, 123 were found to have one of the following chromosomal abnormalities: Trisomy 21, Trisomy 18, Trisomy 13 or Turner syndrome. This study focuses on 40 additional patients who were found to have 'other' rare chromosomal abnormalities such as triploidy, structural chromosomal abnormalities, sex chromosome abnormalities or unusual chromosomal abnormalities (e.g. 47XX + 16), giving an incidence of 1.1 in 1000 for these rare chromosomal abnormalities. Of these 40 pregnancies, only 2 (5%) had an NT measurement of ≥3 mm. The detection rate for combined FTS, using a risk cut-off of ≥1:300, was 35 % (14 of 40 cases). Therefore, 65 % of cases of rarer fetal chromosomal abnormalities had a 'normal' combined FTS risk (<1:300) and 95 % had a 'normal' NT (<3 mm). Conclusion: Traditional FTS methods are unable to identify the vast majority of rare chromosomal abnormalities. Our data do not support the potential detection of rare fetal chromosomal abnormalities as a reason to favour nuchal translucency-based first trimester screening over NIPT.
  • Impact of COVID-19 on the pain and disability of patients with adult spinal deformity.

    Kieser, D C; Bourghli, A; Larrieu, D; Cawley, D T; Hayashi, K; Jakinapally, S; Pizones, J; Boissiere, L; Obeid, I (2021-03-02)
    Purpose: To evaluate the pain and functional effect of the COVID-19 pandemic on patients with ASD reflected by their response to SRS-22, ODI, and SF-36 questionnaires. Methods: Patients who had stable pain and functional outcome scores over the preceding 2 years were enrolled in a local prospectively collected adult spinal deformity (ASD) database. A reanalysis of their SRS22, ODI and SF-36 data 14 days into confinement were compared to their last pre-confinement scores. Results: 89 patients were included in this study (average age 60.7 years, 91% female) with an average time from last FU until confinement of 9.6 months. The ODI total score worsened by 5 points post-confinement with no difference seen in personal care, walking and social life. In contrast, the SRS-22 score showed small improvements in function/activity and satisfaction, but no significant differences for the other domains. Similarly, the SF-36 showed small improvements in physical function, physical and emotional role, vitality and PCS. Conclusion: The global COVID-19 pandemic and ensuing confinement had variable overall effects on ASD patients, without the expected marked worsening. In addition, this study illustrates that the SRS-22 questionnaire is less influenced by environmental and psychological factors than the ODI supporting its objectivity and accuracy in the evaluation of the QoL of ASD patients.
  • Dynamic left ventricular outflow tract gradient resulting from Takotsubo cardiomyopathy ameliorated by intra-aortic balloon pump counterpulsation: a case report.

    O'Brien, Jim; Mahony, Stephen; Byrne, Roger J; Byrne, Robert A (2021-03-03)
    Background: Takotsubo cardiomyopathy is a variant of acute coronary syndrome with characteristic acute left ventricular apical ballooning. Uncommonly, there can be associated left ventricular outflow tract (LVOT) obstruction causing cardiogenic shock refractory to inotropic support. The use of afterload-reducing mechanical support such as intra-aortic balloon pump (IABP) counterpulsation is not routinely employed in instances of this kind. Case summary: In our case report, we describe a 66-year-old female with acute Takotsubo cardiomyopathy and associated LVOT obstruction which failed to respond to high-dose dobutamine and whose clinical trajectory was worsened by fast atrial fibrillation with rapid ventricular response. Within 24 h of admission, the patient had an IABP placed which rapidly improved her haemodynamics. Two days later, IABP was removed and within 6 days of admission, apical ballooning and LVOT obstruction had fully recovered. Conclusion: We recommend early use of mechanical support with IABP counterpulsation to expedite recovery in patients with acute Takotsubo cardiomyopathy with associated LVOT obstruction.

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