Technological University Dublin - Tallaght Campus

Background Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with recurrent nodules and abscesses that culminate in purulent discharge and scarring. It has significant physical, psychological and financial impact. Objectives This study plans to analyse patient costs associated with HS. Direct costs include prescription items. Indirect or out‐of‐pocket costs include dressings, analgesia, and healthcare‐related travel costs. This study will also assess disease impact on quality‐of‐life (QOL). Methods Patients with HS diagnosis attending dermatology OPD at our public tertiary centre were invited to participate. Ethical approval was secured, and informed consent was obtained. Participants completed an anonymous survey which was analysed to identify costs associated with HS as well as demographics and QOL impact. Results A total of 25 patients completed the survey; median age was 29% and 80% were female. Median time from HS onset to diagnosis was 2 years, with 24% waiting >10 years to be diagnosed. In the past 3 months, 20% spent >€200 in both categories; prescription and non‐prescription items. In the non‐prescription category, 36% of patients reported expenditure >€100 in the past 3 months. Dressings were the most common out‐of‐pocket expense (in 15/25 patients), followed by analgesia and protective clothing. Attendance at medical appointments cost 24% of patients €50–€200. Four participants reported difficulty accessing HS treatments due to associated costs. Mean number of absence days from work/education as result of HS was 8.7 in the past 3 months. Two patients reported being on disability allowance, and two on unemployment benefit as result of their skin disorder. In the QOL question; 96% reported disease impact on QOL, and 11 participants reported that it affected their life ‘very much’. Conclusions HS is a chronic inflammatory skin condition with significant financial burden alongside the well‐analysed biopsychosocial disease impact. Financial burden can be divided into direct prescription costs and indirect costs such as non‐prescription items, protective clothing and travel costs which we have explored in this study. Further research is needed in this area to identify and optimise both the financial and QOL implications of HS in acute flares and chronic disease management.

Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions. To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND). Members of the ERN-RND working group developed a questionnaire considering child-to-adult transition issues and procedures in current clinical practice. The questionnaire included 20 questions and was sent to members of the health care providers (HCPs) participating in the network. Twenty ERN-RND members (75% adult neurologists; 25% pediatricians; 5% nurses or study coordinators) responded to the survey, representing 10 European countries. Transition usually occurs between 16 and 18 years of age, but 55% of pediatric HCPs continue to care for their patients until they reach 40 years of age or older. In 5/20 ERN-RND centers, a standardized procedure managing transition is currently adopted, whereas in the remaining centers, the transition from youth to adult service is usually assisted by pediatricians as part of their clinical practice. This survey demonstrated significant variations in clinical practice between different centers within the ERN-RND network. It provided valuable data on existing transition programs and highlighted key challenges in managing transitions for patients with rare neurological disorders.

Background and purpose Tay−Sachs disease is a rare and often fatal, autosomal recessive, lysosomal storage disease. Deficiency in β‐hexosaminidase leads to accumulation of GM2 ganglioside resulting in neuronal swelling and degeneration. Typical onset is in infancy with developmental regression and early death. Late‐onset Tay−Sachs disease (LOTS) is extremely rare, especially in the non‐Ashkenazi Jewish population, and is characterized by a more indolent presentation typically encompassing features of cerebellar and anterior horn cell dysfunction in addition to extrapyramidal and neuropsychiatric symptoms. Cases A case series of four unrelated patients of non‐Ashkenazi Jewish origin with a predominantly, and in some cases pure, neuromuscular phenotype with evidence of a motor neuronopathy on electromyography is presented. Cerebellar atrophy, reported to be a ubiquitous feature in LOTS, was absent in all patients. Conclusion This case series provides evidence to support a pure neuromuscular phenotype in LOTS, which should be considered in the differential diagnosis of anterior horn cell disorders.

It has often been reported that mental exertion, presumably leading to mental fatigue, can negatively affect exercise performance; however, recent findings have questioned the strength of the effect. To further complicate this issue, an overlooked problem might be the presence of publication bias in studies using underpowered designs, which is known to inflate false positive report probability and effect size estimates. Altogether, the presence of bias is likely to reduce the evidential value of the published literature on this topic, although it is unknown to what extent. The purpose of the current work was to assess the evidential value of studies published to date on the effect of mental exertion on exercise performance by assessing the presence of publication bias and the observed statistical power achieved by these studies. A traditional meta-analysis revealed a Cohen’s dz effect size of − 0.54, 95% CI [− 0.68, − 0.40], p < .001. However, when we applied methods for estimating and correcting for publication bias (based on funnel plot asymmetry and observed p-values), we found that the bias-corrected effect size became negligible with most of publication-bias methods and decreased to − 0.36 in the more optimistic of all the scenarios. A robust Bayesian meta-analysis found strong evidence in favor of publication bias, BFpb > 1000, and inconclusive evidence in favor of the effect, adjusted dz = 0.01, 95% CrI [− 0.46, 0.37], BF10 = 0.90. Furthermore, the median observed statistical power assuming the unadjusted meta-analytic effect size (i.e., − 0.54) as the true effect size was 39% (min = 19%, max = 96%), indicating that, on average, these studies only had a 39% chance of observing a significant result if the true effect was Cohen’s dz = − 0.54. If the more optimistic adjusted effect size (− 0.36) was assumed as the true effect, the median statistical power was just 20%. We conclude that the current literature is a useful case study for illustrating the dangers of conducting underpowered studies to detect the effect size of interest.

Objectives To explore the differences in training and match load in English Premier League (EPL) 1st team and U23 players. Identifying differences in relative and absolute physical outputs in relation to Maximal Aerobic Speed (MAS) and Maximal Sprint Speed (MSS) and how this informs monitoring and training prescription. Methods Two groups of full-time professional football players (1st team, n = 24 and U23 squad, n = 27) participated in this study. Training and match data were categorised into weekly blocks from Monday to Sunday. Each player's weekly total was then averaged to provide a squad average for each metric examined. Results Match analysis identified significantly higher distance covered above 120% MAS and distance between 120% MAS and 85% MSS ( p = .04, effect size [ES] = 0.64; p < .01, ES = 1.13) for the 1st team. Distance above 85% MSS was significantly higher for the U23's ( p < .01, ES = 2.92). Training and match data during one-match weeks displayed significantly higher differences in all high-speed variables for 1st team players compared to U23 players ( p ≤ .05, ES = 0.82–1.78). Analysis of training and match data during a two-match week displayed no significant differences for all physical variables ( p > .05). Conclusions Practitioners should consider the utilisation of individual relative thresholds to identify differences between physical performance variables during training and matches for 1st team and U23 players. Utilising these comparisons to inform training design, could maximise players physical development and potential for successful transition. Importantly, these findings relate to only one EPL club and therefore practitioners should assess their own players’ relative training and game outputs.

Aim: Hereditary sensory neuropathy (HSN) 1E is a neurodegenerative disorder caused by pathogenic variants in DNA methyltransferase 1 (DNMT1). It is characterised by sensorineural deafness, sensory neuropathy and cognitive decline. Variants in DNMT1 are also associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy. Methods: A 42 year old man presented with imbalance, lancinating pains, numerous paucisymptomatic injuries, progressive deafness since his mid-20s, mild cognitive decline and apathy. Examination revealed abnormalities of eye movements, distal sensory loss to all modalities, areflexia without weakness and lower limb ataxia. MRI brain and FDG-PET scan demonstrated biparietal and cerebellar atrophy/ hypometabolism. Whole exome sequencing detected a heterozygous likely pathogenic missense variant in DNMT1, c.1289G>A, p.Cys430Tyr. Cochlear implant was performed at 44 years for the bilateral high frequency sensorineural hearing loss with improvement in hearing and day-to-day function. Results and conclusion: We describe a novel variant in DNMT1 and confirm that an overlapping HSN1E-cerebellar phenotype can occur. Only one prior case of cochlear implant in HSN1E has been reported to date but this case adds to that literature, suggesting that cochlear implant can be successful in such patients. We further explore the clinical and radiological signature of the cognitive syndrome associated with this disorder. This article is protected by copyright. All rights reserved.

Background Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome. Methods A retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years. Results Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0–12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function. Conclusions Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.

Hyaluronic acid (HA) is a naturally occurring mucopolysaccharide that, due to its inherent bioactivity and extracellular matrix-like structure, has the potential to be utilised extensively in tissue engineering. However, this glycosaminoglycan lacks the properties required for cellular adhesion and photo-crosslinking by UV light, which significantly hinders this polymers applicability. This research presents a method for modifying hyaluronic acid via thiolation and methacrylation to generate a novel photo-crosslinkable polymer with improved physicochemical properties, biocompatibility and the potential to customize biodegradability according to the ratio of monomers used. A decrease in stiffness proportional to increasing thiol concentration was observed when testing the compressive strength of hydrogels. Conversely, it was noted that the storage moduli of hydrogels increased proportionally to thiol concentration indicating a greater degree of cross-linking with the addition of thiol. The addition of thiol to HA increased the biocompatibility of the material in both neuronal and glial cell lines and improved the degradability of methacrylated HA. Due to the enhanced physicochemical properties and biocompatibility imparted by the introduction of thiolated HA, this novel hydrogel system could have numerous bioengineering applications.

Background Carriage of HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADA) in patients with Crohn’s Disease (CD) receiving anti-TNF therapy. The presence of ADA is not uniformly associated with anti-TNF therapy failure as patients with adequate trough drug concentrations, even where ADA are present, can maintain therapy response. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of anti-TNF therapy evaluated by drug persistence in routine clinical practice. Methods A multi-centre retrospective study of IBD patients treated with anti-TNF therapy was performed. HLA-DQA1*05 genotypes were generated for each included patient by imputation from whole genome sequence using HIBAG. Only outcome of first anti-TNF therapy received by patients was evaluated in this study. Study primary endpoint was anti-TNF therapy persistence, expressed as time to discontinuation of anti-TNF therapy, segregated by HLA-DQA1*05 allele genotype. Patients discontinuing anti-TNF therapy due to primary or secondary loss of response or due to side-effects were considered therapy failures. Statistical analysis was performed using survival analysis and multivariate cox logistic regression with effect of covariates on outcome expressed as odds ratios (OR). Results 921 IBD patients were identified with 877 included in the study population. Baseline demographics for the entire cohort and segregated by HLA-DQA1*05 allele status are summarised in Figure 1. In the study population, 543 (62%) had no copy, 281 (32%) one copy and 53 (6%) two copies of HLA-DQA1*05 allele. Median time to anti-TNF therapy discontinuation in patients with 2 copies of HLA-DQA1*05 allele was significantly shorter compared to patients with 1 or no copy at 700-days follow-up: 418 versus 513 versus 541 days respectively, p=0.007 (Figure 2) with similar results observed at 2000-days follow-up (p=0.04). In a multivariate regression, factors independently associated with time to anti-TNF therapy discontinuation included: carriage of HLA-DQA1*05 allele OR 1.2, p=0.02; male gender OR 1.6, p=4.2 x 10-5; CD phenotype OR 0.7, p=0.009; and anti-TNF therapy type (infliximab) OR 1.5, p=0.002. Concomitant immunomodulator use was not associated with time to anti-TNF therapy discontinuation in this model, OR 0.97, p=0.84. Conclusion Carriage of two HLA-DQA1*05 alleles is associated with a less favorable outcome of anti-TNF therapy with shorter time to therapy discontinuation. Carriage of one HLA-DQA1*05 allele is not associated with outcome of anti-TNF therapy. Assessing HLA-DQA1*05 genotype has value in routine clinical practice as HLA-DQA1*05 homozygotes are at increased risk of anti-TNF failure which should be a consideration in IBD therapy selection.

Ladies Gaelic football (LGF) is a traditional , amateur Gaelic sport played by female athletes. LGF is an invasion-based field sport involving high-intensity, intermittent match play. There is currently a paucity of research on intercounty (elite level) LGF despite a growing interest in the male version of the game. This article aims to provide strength and conditioning recommendations for LGF with particular focus on the intercounty level of play. Recommendations within this article include a needs analysis, female injury epidemiology , physical and physiological demands, female physiology, strength training, and specific conditioning guidelines based on the sport. Additional recommendations include an LGF-specific testing battery, a proposed periodization cycle, and sports-specific speed and agility development.

Purpose The current study compared specific positional and temporal running performance profiles of elite and sub-elite hurling players during competitive match-play. Methods Running performance data were obtained during match-play using GPS technology (GPEXE lt 18 Hz, Exelio, srl, Udine, Italy) from 53 elite and 81 sub-elite hurlers resulting in 524 total data sets (elite n = 200; sub-elite n = 324). Running performance data consisted of total distance [TD], high-speed running [HSR], sprint distance, accelerations [n], maximal speed [km·h− 1], relative total distance (RTD), relative high-speed running (RHSR), relative sprint distance (RSD), and relative accelerations. All data were analysed across level and positions. Additionally, HSR and RHSR were analysed across halves of play. Multiple two-way ANOVAs determined the effect of two fixed factors (level and position) on each of the running performance variables. Furthermore, two three-way ANOVAs determined the effect of level, position and halves on HSR and RHSR. Results Elite level players covered a greater relative TD (η² = 0.037; small) and relative HSR (η² = 0.023; small) across positional lines of half-back (η² = 0.008, small), midfield (η² = 0.025, small) and half-forward (η² = 0.009, small) when compared to their sub-elite counterparts. Temporal decrements in relative HSR of 11.3% at elite level and 5.7% at sub-elite level were observed across halves of match-play. Specifically, across the positional lines of half-back (13.1 v 2.7%), midfield (9.7 v 9.1%) and half-forward (11.9 v 6.1%) elite level players were observed to have a higher decrement in relative HSR when compared to sub-elite players. Conclusion The current data are the first to show differences in positional running performance between standards of play within hurling. These normative data provide additional considerations for hurling coaches with respect to transitioning players from sub-elite to elite level of play.

Known methodological issues such as publication bias, questionable research practices and studies with underpowered designs are known to decrease the replicability of study findings. The presence of such issues has been widely established across different research fields, especially in psychology. Their presence raised the first concerns that the replicability of study findings could be low and led researchers to conduct large replication projects. These replication projects revealed that a significant portion of original study findings could not be replicated, giving rise to the conceptualization of the replication crisis. Although previous research in the field of sports and exercise science has identified the first warning signs, such as an overwhelming proportion of significant findings, small sample sizes and lack of data availability, their possible consequences for the replicability of our field have been overlooked. We discuss the consequences of the above issues on the replicability of our field and offer potential solutions to improve replicability.

Background: Progressive supranuclear palsy (PSP)-Richardson's syndrome (RS) presents with a distinctive clinical phenotype of supranuclear ophthalmoplegia, parkinsonism, postural instability with falls, and cognitive impairment. Several rare neurological conditions have been described that mimic PSP, and the co-occurrence of dual pathologies has also been described. Cases: In this article, we present 2 cases of patients who presented with a parkinsonian phenotype suggestive of PSP-RS. In 1 case, a family history and early levodopa-induced chorea led to testing for Huntington's disease, and a pathogenic HTT mutation was found. In the second case, magnetic resonance imaging findings led to genetic confirmation of a pathogenic FMR1 mutation. Conclusions: These observations raised the possibility that HD and fragile-X tremor-ataxia syndrome may on occasion present with PSP-RS. Alternatively, and perhaps more likely, is the co-occurrence of 2 rare neurodegenerative conditions. Neuropathological studies of cases involving complex phenotypes in rare genetic conditions are required to better understand the likely pathologies in cases such as these.

The current review focuses on Gaelic football literature providing an insight into the physical characteristics of players, the demands of match-play, the injury profile, and nutritional considerations within the game. Since the first review of Gaelic football in 2001, an increased understanding of match dynamics has taken place through the application of movement analysis technology. In recent years, the evolution of the application of sport science provisions within Gaelic football has increased. This has resulted in researchers attempting to bridge the gap between the scientific laboratory and the applied practitioner. Overall, intermittent aerobic fitness remains important during competition, along with upper and lower body strength, speed and jump-based characteristics, with positional and seasonal variations present in Gaelic football. The stochastic nature of Gaelic football means distances covered during match-play will have an inherent positional profile, with gradual reductions in match-play running performance frequently observed. Monitoring training loads in combination with response variables, such as well-being, can allow practitioners to achieve optimal dose and response characteristics via training regimes. The risk of injury to elite Gaelic football players is significantly greater during match-play, compared to during training. 70% of injuries occur to the lower limb region, with hamstring and knee injuries being the most common. Furthermore, specific findings show that training days elicit the greatest deficits between intake and expenditure, as such practitioners should target specific nutritional interventions to ensure that players are optimally loaded for the energetic requirements of these sessions. The current review can provide information to coaches and practitioners around position-specific physical qualities, match-play demands, and concurrently, support the training process within Gaelic football.

The current investigation aimed to understand the differing positional demands across two elite rugby union competitions, with special reference to high-intensity effort (HIE) and repeated high-intensity effort (RHIE) activity. Four hundred and forty-one (n = 441) individual game files from thirty-five competitive games from the European Rugby Champions Cup (tier 1; n = 8) and PRO12 League (tier 2; n = 24) were analysed. Players' locomotor profiles were recorded using wearable global positioning system microtechnology (10 Hz Catapult S5, Catapult Innovations, Australia). Locomotor activities were classified as running (≥4.4 m•s −1), high-speed running (≥5.5 m•s −1), accelerations (≥2 m•s −2) and decelerations (≤−2 m•s −2). Data was gathered on collisions (≥4 g −1), high-intensity efforts (HIE), repeated high-intensity efforts (RHIE), average number of efforts within a RHIE bout (n) and maximal number of efforts within a RHIE bout (n). Overall locomotor differences between competitions were trivial to small in nature, with tier 1 competition associated with a larger number of RHIE bouts (6.5 ± 1.4 vs. 5.7 ± 1.5, effect size, ES = 0.55) and efforts per bout (3.0 ± 1.1 vs. 2.4 ± 1.2, ES = 0.52). Collisions comprised a greater proportion of total HIE for forwards within tier 1 competition compared to tier 2 competition. The hooker (mean difference: 4 [−10 to 14]; ES = 0.30, small), lock (mean difference: 5 [−12 to 23]; ES = 0.36, small) and backrow (mean difference: 8 [−10 to 15]; ES = 0.54, small) positions engaged in more collisions during tier 1 competition compared to tier 2 competition. These findings can be used by athletic performance staff to design game-specific drills and recovery strategies during different competition weeks to ensure players are appropriately prepared for the differing demands of elite rugby competition.

The true differences between barefoot and shod running are difficult to directly compare because of the concomitant change to a mid/forefoot footfall pattern that typically occurs during barefoot running. The purpose of this study was to compare isolated effects of footwear structure and cushioning on running mechanics in habitual mid/forefoot runners running shod (SHOD), barefoot (BF), and barefoot on a foam surface (BF+FOAM). Ten habitually shod mid/forefoot runners were recruited (male = 8, female = 2). Repeated measures ANOVA (α = 0.05) revealed differences between conditions for only vertical peak active force, contact time, negative and total ankle joint work, and peak dorsiflexion angle. Post hoc tests revealed that BF+FOAM resulted in smaller vertical active peak magnitude and instantaneous vertical loading rate than SHOD. SHOD resulted in lower total ankle joint work than BF and BF+FOAM. BF+FOAM resulted in lower negative ankle joint work than either BF or SHOD. Contact time was shorter with BF than BF+FOAM or SHOD. Peak dorsiflexion angle was smaller in SHOD than BF. No other differences in sagittal joint kinematics, kinetics, or ground reaction forces were observed. These overall similarities in running mechanics between SHOD and BF+FOAM question the effects of footwear structure on habituated mid/forefoot running described previously.

Introduction Interleukin 5 (IL-5) inhibitors are an important therapeutic advance in the management of severe, refractory, eosinophilic asthma. However, their utilisation should be targeted to maximise their benefits. This study used multisite, centralised, national data collected over 18 months to perform an observational integrated, retrospective, cohort study of selection criteria for initiation and continuation of IL-5 inhibitor treatment in Ireland. Materials/patients and methods We used data from 230 patients who were given anti-IL-5 monoclonal therapy (reslizumab, mepolizumab or benralizumab) in Ireland between 2018 and 2020. Reimbursement of these drugs in Ireland requires fulfilling eligibility criteria defined by the Acute Hospitals Drugs Management Programme with continued reimbursement requiring ongoing submission of clinical data demonstrating clinical effectiveness. Results IL-5 inhibitor use for 18 months was associated with a total reduction in asthma-associated hospital admissions of 108 (p=0.036) and in non-hospital exacerbations of 85 in 18 months (p=0.014). Respiratory-associated GP visits were reduced from 637 in 12 months to 89 at 6 months and 210 at 18 months of treatment (p<0.001). Oral corticosteroid requirement was reduced or stopped entirely (p<0.001). Subgroup analysis of one site replicated these results and showed a significant reduction in the Asthma Control Questionnaire Score (p<0.001) Conclusions Selected patients continued on IL-5 treatment to 18 months had significantly reduced exacerbations, GP visits, oral corticosteroid use and asthma-associated hospitalisations. These results show that anti-IL-5 therapy, in carefully selected and monitored patients with asthma, results in significant improvements in clinical outcomes in a real-world setting.

The unfolded protein response has recently been implicated as a mechanism by which 1,10-phenanthroline-containing coordination compounds trigger cell death. We explored the interaction of two such compounds—one containing copper and one containing manganese—with endoplasmic reticulum (ER) stress. Pretreatment with anisomycin significantly enhanced the cytotoxic activity of both metal-based compounds in A2780, but only the copper-based compound in A549 cells. The effects of pretreatment with tunicamycin were dependent on the nature of the metal center in the compounds. In A2780 cells, the cytotoxic action of the copper compound was reduced by tunicamycin only at high concentration. In contrast, in A549 cells the efficacy of the manganese compound cells was reduced at all tested concentrations. Intriguingly, some impact of free 1,10-phenanthroline was also observed in A549 cells. These results are discussed in the context of the emerging evidence that the ER plays a role in the cytotoxic action of 1,10-phenanthroline-based compounds.