Research by staff affiliated to St. James's Hospital

Recent Submissions

  • The Omentum in Obesity-Associated Cancer: A Hindrance to Effective Natural Killer Cell Migration towards Tumour Which Can Be Overcome by CX3CR1 Antagonism.

    Mylod, Eimear; O'Connell, Fiona; Donlon, Noel E; Butler, Christine; Reynolds, John V; Lysaght, Joanne; Conroy, Melissa J (2021-12-23)
  • Title: Understanding a Low Vitamin D State in the Context of COVID-19.

    McCarroll, Kevin; Healy, Martin; O'Shea, Paula M; Kenny, Rose Anne; Faul, John L; Walsh, James Bernard; McCartney, Daniel; Laird, Eamon; Byrne, Declan (2022-03-04)
    While a low vitamin D state has been associated with an increased risk of infection by SARS-CoV-2 in addition to an increased severity of COVID-19 disease, a causal role is not yet established. Here, we review the evidence relating to i) vitamin D and its role in SARS-CoV-2 infection and COVID-19 disease ii) the vitamin D status in the Irish adult population iii) the use of supplemental vitamin D to treat a deficient status and iv) the application of the Bradford-Hill causation criteria. We conclude that reverse causality probably makes a minimal contribution to the presence of low vitamin D states in the setting of COVID-19. Applying the Bradford-Hill criteria, however, the collective literature supports a causal association between low vitamin D status, SARS-CoV-2 infection, and severe COVID-19 (respiratory failure, requirement for ventilation and mortality). A biologically plausible rationale exists for these findings, given vitamin D's role in immune regulation. The thresholds which define low, deficient, and replete vitamin D states vary according to the disease studied, underscoring the complexities for determining the goals for supplementation. All are currently unknown in the setting of COVID-19. The design of vitamin D randomised controlled trials is notoriously problematic and these trials commonly fail for a number of behavioural and methodological reasons. In Ireland, as in most other countries, low vitamin D status is common in older adults, adults in institutions, and with obesity, dark skin, low UVB exposure, diabetes and low socio-economic status. Physiological vitamin D levels for optimal immune function are considerably higher than those that can be achieved from food and sunlight exposure alone in Ireland. A window exists in which a significant number of adults could benefit from vitamin D supplementation, not least because of recent data demonstrating an association between vitamin D status and COVID-19. During the COVID pandemic, we believe that supplementation with 20-25ug (800-1000 IU)/day or more may be required for adults with apparently normal immune systems to improve immunity against SARS-CoV-2. We expect that higher monitored doses of 37.5-50 ug (1,500-2,000)/day may be needed for vulnerable groups (e.g., those with obesity, darker skin, diabetes mellitus and older adults). Such doses are within the safe daily intakes cited by international advisory agencies.
  • Should MRI Be the Imaging Modality of Choice in Suspected Appendicitis During Pregnancy?

    Donlon, N E; Kelly, M E; Davern, M; Sheppard, A; Nugent, T; Durand, M; Mehigan, B J; Larkin, J O; McCormick, P H (2019-12-16)
    Aim The aim of this review was to evaluate the efficacy of magnetic resonance imaging (MRI) in determining appendicitis during pregnancy. Methods We retrospectively reviewed the clinical course for all pregnant patients with suspected appendicitis from 2013-2018. We evaluated the efficacy of MRI and Alvarado scoring and its impact on management. Results Twenty-nine pregnant patients with suspected appendicitis had an MRI. The majority (90%, n=26/29) had normal diagnostics with two patients (10.3%) having findings consistent with acute appendicitis. Two other patients proceeded to laparoscopy, one with an inconclusive MRI, and one patient with clinical appendicitis. We found no accurate correlation between pregnancy and Alvarado scoring. Conclusion MRI is a safe adjunct in accurately diagnosing appendicitis in pregnancy. Its routine use could help reduce rates of negative appendectomies and the potential risk to maternal and fetal health.
  • Leptomeningeal Relapse of Embryonal Rhabdomyosarcoma after 15 years.

    Chew, S; Gleeson, J P; McCarthy, A; Watson, G A; O'Dwyer, R; Nicholson, S; Capra, M; Owens, C; McDermott, M; Daly, P; et al. (2020-12-16)
    Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour of childhood, albeit accounting for only 3-4% of all childhood cancers. Embryonal RMS accounts for around 60% of all RMS cases, usually occurs in children less than 5 years of age and commonly originates from the head, neck or urogenital system. Alveolar RMS is responsible for about 21% of cases and tends to affect the trunk and limbs. Other less common subtypes include botyroid and spindle cell RMS.1 The introduction of a combined modality treatment approach has resulted in improved patient outcomes, with over 70% of patients with localised RMS cured of their disease. Disease relapse tends to happen early and is associated with a poor prognosis, but late relapse is poorly studied and understood. We present the case of a very late relapse of RMS in an unusual location.
  • Case Report: Acquired collagenoma on the dorsum of the foot.

    O'Donohoe, Patrick; Theopold, Christoph; McMenamin, Mairin (2022-03-10)
    Collagenoma is a rare benign skin lesion classified as a hamartomatous proliferation of normal collagen fibres and varying amounts of elastic fibres. They most frequently occur on the arms or trunk and may present as solitary or multiple lesions, as part of a syndrome (such as Cowden Syndrome, Tuberous Sclerosis, or MEN1) or sporadic and of varying sizes. Herein, we report on a case of large acquired collagenomas found in an unusual location on the dorsum of both feet.
  • Changing demographics and immunity to vaccine preventable diseases in people with HIV in Ireland.

    Kelleher, M; Coughlan, S; Crowley, B; O'Reilly, E J; Bergin, C; Kerr, Colm (2022-06-29)
    Background: HIV infection is associated with an increased risk of morbidity and mortality from vaccine preventable infections. This research describes, in the context of changing patient demographics, the seroprevalence of vaccine preventable viral infections among attendees of the largest centre for HIV positive patients in Ireland. Methods: Baseline serum IgG results for measles, mumps, rubella, varicella zoster virus (VZV) & hepatitis A, as well as hepatitis B sAg, cAb and sAb results, were retrieved for 2534 clinic attendees attending in 2018. Results were available for between 990 and 2363 attendees (39-93%), depending on the test, and were compared with 2013 clinic data. Results: There was a 35% increase in attendees in 2018 when compared to 2013. The largest increase was in attendees of South American origin. In 2018, males accounted for 73% of the entire cohort and the HIV acquisition risk for 48% of attendees was MSM. 47% of attendees were originally from Ireland. Among those tested, 33% were susceptible to at least one component of the MMR vaccine. 5% were VZV non-immune (significantly associated with younger age and the acquisition risk status of injection drug use). 21% were hepatitis A non-immune (significantly associated with younger age and being of European or South American origin). 32% were hepatitis B cAb seropositive (significantly associated with older age, injection drug use status and being originally from Africa). 3% demonstrated hepatitis B sAg positivity. 64% had hepatitis B sAb ≥ 10mIU. Conclusion: In a cohort of attendees to an HIV clinic in a large urban setting, the susceptibility to several common vaccine preventable viral infections, in particular MMR and hepatitis A and B, was high. These results highlight the importance of proactive screening and immunisation to help protect this high risk patient group against vaccine preventable diseases.
  • The Incidence of Venous Thromboembolism in Critically Ill Patients with SARS-CoV-2 Infection Compared with Critically Ill Influenza and Community-Acquired Pneumonia Patients: A Retrospective Chart Review.

    Boyd, Sean; Sheng Loh, Kai; Lynch, Jessie; Muzzammil, Saad; Marsh, Hannah; Masoud, Mustafa; Bin Ihsan, Salman; martin-loeches, Prof. Ignacio; Alrashed, Dhari (2022-06-08)
    The rate of venous thromboembolism in COVID-19 patients has been reported to be 30% (deep vein thrombosis 20% and pulmonary embolism 18%). This has been shown to be higher in COVID-19 patients admitted to the ICU. Prophylactic anticoagulation may be sufficient at ward level, but not in intensive care. A retrospective chart review was undertaken in a large university hospital. The review included 276 patients from COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia groups. The timeframe included patients admitted between 23 February 2014 and 12 May 2021. Clinical characteristics, outcomes, blood results, rates of venous thromboembolism, and anticoagulation status were recorded. The incidence of venous thromboembolism in COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia was 10.91%, 13.69%, 13.33%, and 6.81%, respectively (p = 0.481). The incidence of pulmonary embolism was 7.27%, 10.95%, 3.33%, and 5.68%, respectively (p = 0.350). The incidence of deep vein thrombosis was 5.45%, 5.48%, 10.00%, and 1.14%, respectively (p = 0.117). Although most patients were prophylactically anticoagulated, venous thromboembolism still occurred. Venous thromboembolism remains an important differential to consider in critically ill COVID-19 patients. The current literature does not advise therapeutic anticoagulation for thromboprophylaxis in the ICU.
  • The Incidence of Venous Thromboembolism in Critically Ill Patients with SARS-CoV-2 Infection Compared with Critically Ill Influenza and Community-Acquired Pneumonia Patients: A Retrospective Chart Review.

    Boyd, Sean; Sheng Loh, Kai; Lynch, Jessie; Muzzammil, Saad; Marsh, Hannah; Masoud, Mustafa; Bin Ihsan, Salman; martin-loeches, Prof. Ignacio; Alrashed, Dhari (2022-06-08)
    The rate of venous thromboembolism in COVID-19 patients has been reported to be 30% (deep vein thrombosis 20% and pulmonary embolism 18%). This has been shown to be higher in COVID-19 patients admitted to the ICU. Prophylactic anticoagulation may be sufficient at ward level, but not in intensive care. A retrospective chart review was undertaken in a large university hospital. The review included 276 patients from COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia groups. The timeframe included patients admitted between 23 February 2014 and 12 May 2021. Clinical characteristics, outcomes, blood results, rates of venous thromboembolism, and anticoagulation status were recorded. The incidence of venous thromboembolism in COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia was 10.91%, 13.69%, 13.33%, and 6.81%, respectively (p = 0.481). The incidence of pulmonary embolism was 7.27%, 10.95%, 3.33%, and 5.68%, respectively (p = 0.350). The incidence of deep vein thrombosis was 5.45%, 5.48%, 10.00%, and 1.14%, respectively (p = 0.117). Although most patients were prophylactically anticoagulated, venous thromboembolism still occurred. Venous thromboembolism remains an important differential to consider in critically ill COVID-19 patients. The current literature does not advise therapeutic anticoagulation for thromboprophylaxis in the ICU.
  • Scoring the Clinical Frailty Scale in the Emergency Department: The Home FIRsT Experience.

    Thorpe, Owen; McCabe, Elva; Herrero, Elena Marie; Doyle, William Ormiston; Dillon, Aoife; Edge, Lucinda; Flynn, Sinéad; Mullen, Anna; Davis, Aisling; Molamphy, Aoife; et al. (2022-06-01)
    We evaluated predictors of the Clinical Frailty Scale (CFS) scored by an interdisciplinary team (Home FIRsT) performing comprehensive geriatric assessment (CGA) in our Emergency Department (ED). This was a retrospective observational study (service evaluation) utilising ED-based CGA data routinely collected by Home FIRsT between January and October 2020. A linear regression model was computed to establish independent predictors of CFS. This was complemented by a classification and regression tree (CRT) to evaluate the main predictors. There were 799 Home FIRsT episodes, of which 740 were unique patients. The CFS was scored on 658 (89%) (median 4, range 1-8; mean age 81 years, 61% women). Independent predictors of higher CFS were older age (p<0.001), history of dementia (p<0.001), mobility (p≤0.007), disability (p<0.001), and higher acuity of illness (p=0.009). Disability and mobility were the main classifiers in the CRT. Results suggest appropriate CFS scoring informed by functional baseline.
  • Changing demographics and immunity to vaccine preventable diseases in people with HIV in Ireland.

    Kerr, Colm; Kelleher, M; Coughlan, S; Crowley, B; O'Reilly, E J; Bergin, C (2022-06-29)
  • Are Janus kinase inhibitors safe and effective in treating the key clinical domains of psoriatic arthritis? A systematic review and meta-analysis.

    Harkins, Patricia; Burke, Eoghan; Swales, Catherine; Silman, Alan; Conway, Richard (2022-10-02)
    Objectives: Psoriatic arthritis (PsA), is a complex inflammatory arthropathy with a heterogenous spectrum of disease presentation. Despite the vast therapeutic armamentarium, disease control in a considerable proportion of patients is suboptimal. The aim of this study was to assess the safety and efficacy of Janus kinase inhibitors (JAKi), in the management of key clinical domains of PsA including peripheral arthritis, psoriasis, enthesitis and dactylitis. Method: Randomized placebo-controlled trials (RCTs) of JAKi in PsA were identified by a systematic literature search using EMBASE, PubMed and CENTRAL. All included studies underwent meta-analysis. Results: A total of 5 RCTs were included. Patients were randomized to tofacitinib (n = 474), filgotinib (n = 65), upadacitinib (n = 1281) or placebo (n = 937). JAKi treatment was associated with superior efficacy across all primary outcome measures vs placebo: American College of Rheumatology (ACR) 20 (risk ratio [RR] 2.10, [95% CI 1.86-2.37], P < .00001, I2 = 19%); ACR 50 (RR 3.43, [95% CI 2.37-4.96], P < .00001, I2 = 66%); ACR 70 (RR 4.57, [95% CI 1.83-11.44], P = .001, I2 = 82%); Psoriasis Area and Severity Index 75 (RR 2.96, [95% CI 2.44-3.58], P < .00001, I2 = 0%); enthesitis resolution (RR 1.82, [95% CI 1.56-2.12], P < .00001, I2 = 0%); and dactylitis resolution (RR 1.85, [95% CI 1.57-2.16], P < .00001, I2 = 0%). JAKi were associated with an overall increased risk of adverse events (RR 1.14, [95% CI 1.07-1.21], P = .0001, I2 = 0%) with increased risk of infection (RR1.23, [95% CI 1.08-1.39], P = .001, I2 = 0%) vs placebo. Conclusion: This pooled analysis demonstrates the efficacy of JAKi in treating key clinical domains of PsA. However, they are associated with an increased risk of adverse events, including infection. Further studies are required to corroborate these findings and further elucidate the safety profile. Keywords: Janus kinase inhibitors; dactylitis; enthesitis; filgotinib; psoriasis; psoriatic arthritis; tofacitinib; upadacitinib.
  • Persistent endotheliopathy in the pathogenesis of long COVID syndrome.

    Fogarty, Helen; Townsend, Liam; Morrin, Hannah; Ahmad, Azaz; Comerford, Claire; Karampini, Ellie; Englert, Hanna; Byrne, Mary; Bergin, Colm; O'Sullivan, Jamie M; et al. (2021-09-12)
    Background: Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this "long COVID" syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19. Objectives: To assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis. Patients and methods: Fifty patients were reviewed at a median of 68 days following SARS-CoV-2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed. Results: Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI -2.57 to -1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15-416 nM/min), and peak thrombin (p < .0001, 95% CI 39-93 nM) in convalescent COVID-19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with controls (p = .004, 95% CI 0.09-0.57 IU/ml; p = .009, 95% CI 0.06-0.5 IU/ml; p = .04, 95% CI 0.03-0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID-19 (p = .02, 95% CI 0.01-2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6-min walk tests. Conclusions: Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.
  • Motivators and barriers to blood donation among potential donors of African and Caucasian ethnicity.

    Fogarty, Helen; Sardana, Muskan; Sheridan, Luke; Chieng, Phoebe; Kelly, Sarah; Ngwenya, Noel; Sheehan, Ciara; Morris, Kieran; Tuohy, Emma (2022-06-12)
    Background: Minority blood donation, especially from individuals of African ethnicity, is a focus for many countries with diverse populations. As the need for antigen-negative RBC transfusions for patients with Sickle Cell Disease (SCD) continues to grow, inclusion of more African blood donors is essential to ensure this demand is met. Materials and methods: This study aims to explore barriers and motivators to blood donation and awareness of SCD among potential donors of diverse ethnic backgrounds in Ireland. Following ethical approval, patients attending the National Sickle Cell Disease and Thalassemia service at St James's Hospital were invited to share an online anonymous survey within their local communities to achieve snowball-sampling. Results: 387 respondents completed the survey, including 311 non-donors (median age 25 years, 67% female). Ethnic backgrounds included: African or African-Irish (59%), White or Caucasian (25%), Asian (8%), Hispanic or Latino (3%), Middle Eastern (3%), Multiracial or Biracial (2%). The most commonly identified barrier overall was lack of information on blood donation. African respondents were significantly more likely to report lack of information and malaria-related barriers than Caucasians. Motivators also varied across ethnic groups, with African respondents more likely to donate to help someone within their own community or for religious motivators. Awareness of SCD was higher among African respondents. Discussion: While some barriers to blood donation are shared across all ethnic groups including lack of information, notable differences exist between Caucasian and African respondents. Specific actions to recruit and retain African blood donors should focus on these key areas.
  • Obstetric Outcomes in Women with Rheumatic Disease and COVID-19 in the Context of Vaccination Status.

    Maguire, Sinead; Al-Emadi, Samar; Alba, Paula; Aguiar, Mathia Cecilia; Lawati, Talal Al; Alle, Gelsomina; Bermas, Bonnie; Bhana, Suleman; Branimir, Anic; Bulina, Inita; et al. (2022-09-19)
    Objective: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. Methods: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi -square or Fisher's exact test. Results: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2%(n = 2). Conclusion: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.
  • Meningioma uptake of Gallium-PSMA-11 as a pitfall on positron emission tomography/computer tomography.

    Courtney, Michael; Johnston, Ciaran; Nasoodi, Afshin (2021-02-11)
    Prostate cancer is the most common malignancy in men with high incidence of recurrence following treatment. Biochemical recurrence, as indicated by rising PSA levels following successful treatment of the primary disease, is a frequent encounter in routine clinical practice. 68Gallium-PSMA positron emission tomography/computer tomography has been widely accepted as the modality of choice with the highest impact in management of this group of patients. Pitfalls of this diagnostic technique stem from the diversity of histological entities, other than prostate tumour cells, which can demonstrate increased uptake of the radiotracer. We present a case of intracranial uptake of PSMA by meningioma in a patient with BCR, as a pitfall in imaging of prostate cancer. Knowledge of normal distribution of the tracer is of utmost importance when reading positron emission tomography/computer tomography imaging especially given the relative novelty of usage of 68Gallium-PSMA.
  • 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.
  • 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.
  • Progressive resistance training in a post-acute, older, inpatient setting: A randomised controlled feasibility study.

    Coleman, Sinéad A; Cunningham, Conal J; Murphy, Niamh; Feaheny, Jean; Robinson, David; Lannon, Rosaleen; McCarroll, Kevin; Casey, Miriam; Harbison, Joseph; Horgan, N Frances (2021-03-01)
    Objectives: Progressive resistance training can successfully target functional decline in healthy older community-dwelling adults. There are concerns about the safety and acceptance of its use in frail older populations. The aim of this study was to evaluate the feasibility of using progressive resistance training in an older, post-acute, inpatient setting. Methods: A randomised controlled feasibility study was conducted. Appropriate older inpatients undergoing post-acute rehabilitation were recruited. Feasibility measures examined were safety, recruitment, outcome measurement, adherence and retention rates and satisfaction. A range of clinical measures were used to capture changes in body structure and function, activity and participation. Assessments were performed on admission to the study and six weeks later. Results: A sample of 33 patients were included and randomised to the treatment group (n=16) or the control group (n=17). There were no serious adverse events, adherence rates were 63% and retention rates were 82%. While both groups improved between time 1 and 2, there were no significant differences in clinical measures between the groups. Conclusion: Progressive resistance training is a safe and acceptable intervention for use with this population. Further work on the effectiveness of progressive resistance training in this setting is now required.
  • The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG.

    Cahill, Christina; O'Connell, Fiona; Gogan, Karl M; Cox, Donal J; Basdeo, Sharee A; O'Sullivan, Jacintha; Gordon, Stephen V; Keane, Joseph; Phelan, James J (2021-03-13)
    For over 50 years, patients with drug-sensitive and drug-resistant tuberculosis have undergone long, arduous, and complex treatment processes with several antimicrobials. With the prevalence of drug-resistant strains on the rise and new therapies for tuberculosis urgently required, we assessed whether manipulating iron levels in macrophages infected with mycobacteria offered some insight into improving current antimicrobials that are used to treat drug-resistant tuberculosis. We investigated if the iron chelator, desferrioxamine, can support the function of human macrophages treated with an array of second-line antimicrobials, including moxifloxacin, bedaquiline, amikacin, clofazimine, linezolid and cycloserine. Primary human monocyte-derived macrophages were infected with Bacillus Calmette-Guérin (BCG), which is pyrazinamide-resistant, and concomitantly treated for 5 days with desferrioxamine in combination with each one of the second-line tuberculosis antimicrobials. Our data indicate that desferrioxamine used as an adjunctive treatment to bedaquiline significantly reduced the bacterial load in human macrophages infected with BCG. Our findings also reveal a link between enhanced bactericidal activity and increases in specific cytokines, as the addition of desferrioxamine increased levels of IFN-γ, IL-6, and IL-1β in BCG-infected human monocyte-derived macrophages (hMDMs) treated with bedaquiline. These results provide insight, and an in vitro proof-of-concept, that iron chelators may prove an effective adjunctive therapy in combination with current tuberculosis antimicrobials.

View more