• Therapeutics Today October 2021 Number 10

      National Medicines Information Centre, St James's Hospital (SJ) Dublin 8, 2021-10
    • NMIC bulletin Sep 2021, Vol 27; No. 4: Use of Medicines in Breastfeeding Women

      National Medicines Information Centre (2021-09)
    • Therapeutics Today September 2021 Number 9

      National Medicines Information Centre, St James's Hospital (SJ) Dublin 8, 2021-09
    • Therapeutics Today August 2021 Number 8

      National Medicines Information Centre, St James's Hospital (SJ) Dublin 8, 2021-08
    • NMIC bulletin July 2021, Vol 27; No. 3: Questions and Answers on Biosimilars

      National Medicines Information Centre (National Medicines Information Centre, St James's Hospital (SJ) Dublin 8, 2021-07)
    • Therapeutics Today July 2021 Number 7

      National Medicines Information Centre, St James's Hospital (SJ) Dublin 8, 2021-07
    • Incidence of Fat Embolism Syndrome in Femur Fractures and Its Associated Risk Factors over Time-A Systematic Review.

      Lempert, Maximilian; Halvachizadeh, Sascha; Ellanti, Prasad; Pfeifer, Roman; Hax, Jakob; Jensen, Kai O; Pape, Hans-Christoph (2021-06-21)
      Background: Fat embolism (FE) continues to be mentioned as a substantial complication following acute femur fractures. The aim of this systematic review was to test the hypotheses that the incidence of fat embolism syndrome (FES) has decreased since its description and that specific injury patterns predispose to its development. Materials and methods: Data Sources: MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases were searched for articles from 1 January 1960 to 31 December 2019. Study selection: Original articles that provide information on the rate of FES, associated femoral injury patterns, and therapeutic and diagnostic recommendations were included. Data extraction: Two authors independently extracted data using a predesigned form. Statistics: Three different periods were separated based on the diagnostic and treatment changes: Group 1: 1 January 1960-12 December 1979, Group 2: 1 January 1980-1 December 1999, and Group 3: 1 January 2000-31 December 2019, chi-square test, χ2 test for group comparisons of categorical variables, p-value < 0.05. Results: Fifteen articles were included (n = 3095 patients). The incidence of FES decreased over time (Group 1: 7.9%, Group 2: 4.8%, and Group 3: 1.7% (p < 0.001)). FES rate according to injury pattern: unilateral high-energy fractures (2.9%) had a significantly lower FES rate than pathological fractures (3.3%) and bilateral high-energy fractures (4.6%) (p < 0.001). Conclusions: There has been a significant decrease in the incidence of FES over time. The injury pattern impacts the frequency of FES. The diagnostic and therapeutic approach to FES remains highly heterogenic to this day.
    • Assessment of an electronic patient record system on discharge prescribing errors in a Tertiary University Hospital.

      O'Shea, Michael Patrick; Kennedy, Cormac; Relihan, Eileen; Harkin, Kieran; Hennessy, Martina; Barry, Michael (2021-06-21)
      Background: Prescribing error represent a significant source of preventable harm to patients. Prescribing errors at discharge, including omission of pre-admission medications (PAM), are particularly harmful as they frequently propagate following discharge. This study assesses the impact of an educational intervention and introduction of an electronic patient record (EPR) in the same centre on omission of PAM at discharge using a pragmatic design. A survey of newly qualified doctors is used to contextualise findings. Methods: Discharge prescriptions and discharge summaries were reviewed at discharge, and compared to admission medicine lists, using a paper-based chart system. Discrepancies were noted, using Health Information and Quality Authority guidelines for discharge prescribing. An educational intervention was conducted. Further review of discharge prescriptions and discharge summaries took place. Following introduction of an EPR, review of discharge summaries and discharge prescriptions was repeated. A survey was administered to recently qualified doctors (interns), and analysed using descriptive statistics and thematic analysis. Results: Omission of PAM as prescribed or discontinued items at discharge occurs frequently. An educational intervention did not significantly change prescribing error rates (U = 1255.5, p = 0.206). EPR introduction did significantly reduce omission of PAM on discharge prescribing (U = 694, p < 0.001), however there was also a reduction in the rate of deliberate discontinuation of PAM at discharge (U = 1237.5, p = 0.007). Survey results demonstrated that multiple sources are required to develop a discharge prescription. Time pressure, access to documentation and lack of admission medicine reconciliation are frequently cited causes of discharge prescribing error. Conclusion: This study verified passive educational interventions alone do not improve discharge prescribing. Introduction of EPR improved discharge prescribing, but negatively impacted deliberate discontinuation of PAM at discharge. This is attributable to reduced access to key sources of information used in formulating discharge prescriptions, and separation of the discontinuation function from the prescribing function on the EPR discharge application.
    • Correction to: Understanding what matters most to patients in acute care in seven countries, using the flash mob study design.

      van den Ende, Eva S; Schouten, Bo; Kremers, Marjolein N T; Cooksley, Tim; Subbe, Chris P; Weichert, Immo; van Galen, Louise S; Haak, Harm R; Kellett, John; Alsma, Jelmer; et al. (2021-06-18)
    • Therapeutics Today June 2021 Number 6

      National Medicines Information Centre, St James's Hospital (SJ) Dublin 8, 2021-06
    • Polycythemia vera emerging eighteen years after acute myeloid leukemia diagnosis.

      Langabeer, Stephen E; O'Flynn, Derick W; Cahill, Mary R (2021-06)
    • Pulmonary immuno-thrombosis in COVID-19 ARDS pathogenesis.

      O'Donnell, James S; Peyvandi, Flora; Martin-Loeches, Ignacio (2021-05-30)
    • The role of unconventional T cells in COVID-19.

      Orumaa, Kristen; Dunne, Margaret R (2021-05-29)
      COVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.
    • The Role of the Environment and Exposome in Atopic Dermatitis.

      Stefanovic, Nicholas; Irvine, Alan D; Flohr, Carsten (2021-05-21)
      Purpose of review: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children and up to 5% of adults worldwide, contributing to significant disease-related morbidity in this patient cohort. Its aetiopathogenesis is underpinned by multiple factors, including genetic susceptibility, skin barrier defects, a skewed cutaneous immune response and microbiome perturbation in both the skin and the gut. In this review, we aim to examine the biological effects of key environmental exposures (the sum of which is termed the "exposome") at the population, community and individual levels in order to describe their effect on AD pathogenesis. Recent findings: It is now understood that as well as considering the type of environmental exposure with regard to its effect on AD pathogenesis, the dosage and timing of the exposure are both critical domains that may lead to either exacerbation or amelioration of disease. In this review, we consider the effects of population-wide exposures such as climate change, migration and urbanization; community-specific exposures such as air pollution, water hardness and allergic sensitisation; and individual factors such as diet, microbiome alteration, psychosocial stress and the impact of topical and systemic therapy. Summary: This review summarises the interaction of the above environmental factors with the other domains of AD pathogenesis, namely, the inherent genetic defects, the skin barrier, the immune system and the cutaneous and gut microbiota. We specifically emphasise the timing and dosage of exposures and its effect on the cellular and molecular pathways implicated in AD.
    • Globalization, first-foods systems transformations and corporate power: a synthesis of literature and data on the market and political practices of the transnational baby food industry.

      Baker, Phillip; Russ, Katheryn; Kang, Manho; Santos, Thiago M; Neves, Paulo A R; Smith, Julie; Kingston, Gillian; Mialon, Melissa; Lawrence, Mark; Wood, Benjamin; et al. (2021-05-21)
      Background: The global milk formula market has 'boomed' in recent decades, raising serious concerns for breastfeeding, and child and maternal health. Despite these developments, few studies have investigated the global expansion of the baby food industry, nor the market and political practices corporations have used to grow and sustain their markets. In this paper, our aim is to understand the strategies used by the baby food industry to shape 'first-foods systems' across its diverse markets, and in doing so, drive milk formula consumption on a global scale. We used a theoretically guided synthesis review method, which integrated diverse qualitative and quantitative data sources. Results: Global milk formula sales grew from ~US$1.5 billion in 1978 to US$55.6 billion in 2019. This remarkable expansion has occurred along two main historical axes. First, the widening geographical reach of the baby food industry and its marketing practices, both globally and within countries, as corporations have pursued new growth opportunities, especially in the Global South. Second, the broadening of product ranges beyond infant formula, to include an array of follow-up, toddler and specialized formulas for a wider range of age groups and conditions, thereby widening the scope of mother-child populations subject to commodification. Sophisticated marketing techniques have been used to grow and sustain milk formula consumption, including marketing through health systems, mass-media and digital advertising, and novel product innovations backed by corporate science. To enable and sustain this marketing, the industry has engaged in diverse political practices to foster favourable policy, regulatory and knowledge environments. This has included lobbying international and national policy-makers, generating and deploying favourable science, leveraging global trade rules and adopting corporate policies to counter regulatory action by governments. Conclusion: The baby food industry uses integrated market and political strategies to shape first-foods systems in ways that drive and sustain milk formula market expansion, on a global scale. Such practices are a major impediment to global implementation of the International Code of Marketing of Breastmilk Substitutes, and other policy actions to protect, promote and support breastfeeding. New modalities of public health action are needed to negate the political practices of the industry in particular, and ultimately to constrain corporate power over the mother-child breastfeeding dyad.
    • Understanding what matters most to patients in acute care in seven countries, using the flash mob study design.

      van den Ende, Eva S; Schouten, Bo; Kremers, Marjolein N T; Cooksley, Tim; Subbe, Chris P; Weichert, Immo; van Galen, Louise S; Haak, Harm R; Kellett, John; Alsma, Jelmer; et al. (2021-05-19)
      Background: Truly patient-centred care needs to be aligned with what patients consider important, and is highly desirable in the first 24 h of an acute admission, as many decisions are made during this period. However, there is limited knowledge on what matters most to patients in this phase of their hospital stay. The objective of this study was to identify what mattered most to patients in acute care and to assess the patient perspective as to whether their treating doctors were aware of this. Methods: This was a large-scale, qualitative, flash mob study, conducted simultaneously in sixty-six hospitals in seven countries, starting November 14th 2018, ending 50 h later. One thousand eight hundred fifty adults in the first 24 h of an acute medical admission were interviewed on what mattered most to them, why this mattered and whether they felt the treating doctor was aware of this. Results: The most reported answers to "what matters most (and why)?" were 'getting better or being in good health' (why: to be with family/friends or pick-up life again), 'getting home' (why: more comfortable at home or to take care of someone) and 'having a diagnosis' (why: to feel less anxious or insecure). Of all patients, 51.9% felt the treating doctor did not know what mattered most to them. Conclusions: The priorities for acutely admitted patients were ostensibly disease- and care-oriented and thus in line with the hospitals' own priorities. However, answers to why these were important were diverse, more personal, and often related to psychological well-being and relations. A large group of patients felt their treating doctor did not know what mattered most to them. Explicitly asking patients what is important and why, could help healthcare professionals to get to know the person behind the patient, which is essential in delivering patient-centred care.
    • Hypoxia and its impact on the tumour microenvironment of gastroesophageal cancers.

      King, Ross; Hayes, Conall; Donohoe, Claire L; Dunne, Margaret R; Davern, Maria; Donlon, Noel E (2021-05-15)
      The malfeasant role of the hypoxic tumour microenvironment (TME) in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue to be elucidated. Gastroesophageal cancers (GOCs) represent a major burden of worldwide disease, responsible for the deaths of over 1 million people annually. Disentangling the impact of hypoxia in GOCs enables a better overall understanding of the disease pathogenesis while shining a light on novel therapeutic strategies and facilitating precision treatment approaches with the ultimate goal of improving outcomes for patients with these diseases. This review discusses the underlying principles and processes of the hypoxic response and the effect of hypoxia in promoting the hallmarks of cancer in the context of GOCs. We focus on its bidirectional influence on inflammation and how it drives angiogenesis, innate and adaptive immune evasion, metastasis, and the reprogramming of cellular bioenergetics. The contribution of the hypoxic GOC TME to treatment resistance is examined and a brief overview of the pharmacodynamics of hypoxia-targeted therapeutics is given. The principal methods that are used in measuring hypoxia and how they may enhance prognostication or provide rationale for individually tailored management in the case of tumours with significant hypoxic regions are also discussed.
    • Predictors of hospitalization in patients with rheumatic disease and COVID-19 in Ireland: data from the COVID-19 global rheumatology alliance registry.

      Conway, Richard; Nikiphorou, Elena; Demetriou, Christiana A; Low, Candice; Leamy, Kelly; Ryan, John G; Kavanagh, Ronan; Fraser, Alexander D; Carey, John J; O'Connell, Paul; et al. (2021-05-13)
      Objectives: Given the limited data regarding the risk of hospitalization in patients with rheumatic disease and coronavirus disease 2019 (COVID-19) in Ireland, we used the COVID-19 Global Rheumatology Alliance (GRA) registry data to study outcomes and their predictors. The primary objective was to explore potential predictors of hospitalization. Methods: We examined data on patients and their disease-related characteristics entered in the COVID-19 GRA provider registry from Ireland (from 24 March 2020 to 31 August 2020). Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with hospitalization. Results: Of 105 patients, 47 (45.6%) were hospitalized and 10 (9.5%) died. Multivariable logistic regression analysis showed that age [odds ratio (OR) = 1.06, 95% CI 1.01, 1.10], number of co-morbidities (OR = 1.93, 95% CI 1.11, 3.35) and glucocorticoid use (OR = 15.01, 95% CI 1.77, 127.16) were significantly associated with hospitalization. A diagnosis of inflammatory arthritis was associated with lower odds of hospitalization (OR = 0.09, 95% CI 0.02, 0.32). Conclusion: Increasing age, co-morbidity burden and glucocorticoid use were associated with hospitalization, whereas a diagnosis of inflammatory arthritis was associated with lower odds of hospitalization.
    • Evaluation of the risk factors for venous thromboembolism post splenectomy - A ten year retrospective cohort study in St James's hospital.

      Abduljalil, Manal; Saunders, Jean; Doherty, Dearbhla; Dicks, Marthinus; Maher, Catherine; Mehigan, Brian; Flavin, Richard; Flynn, Catherine M (2021-05-08)
      Background: Splenectomy is a surgical intervention for a variety of indications; benign and malignant. Complications of this procedure include Venous thromboembolism (VTE) and infection. The incidence of VTE post-surgery has been reported between 0.8%-3% depending on the type of surgery. A higher incidence of abdominal VTE was reported post splenectomy (6-11%). However, there is limited literature regarding the risk factors for post splenectomy VTE and the optimal strategy for thromboprophylaxis. Objective: The primary objective of the study was to evaluate the incidence of VTE post splenectomy and to identify the pre-operative, intra-operative and post-operative risk factors. The secondary objective was to assess the local compliance with post-splenectomy prophylactic antibiotics and vaccination protocols. Methods: We conducted a retrospective observational study. All patients who had a splenectomy in St James's Hospital between January 2007 and June 2017 were included and reviewed. Statistical analysis was carried out using SPSS statistical package. Results: 85 patients were involved in the study. The main indications for splenectomy were benign haematology, malignant haematology, solid tumours, traumatic and spontaneous rupture. 6/85 patients developed VTE (7.06%).High BMI ≥ 30 was associated with increased risk of VTE (p = 0.007), while the use of post-operative prophylactic anticoagulation was associated with reduced risk (p = 0.005). Other factors including age >50 years, female gender, presence of active malignancy and splenomegaly were associated with increased VTE risk with no statistical significance. All VTE's occurred in elective versus emergency splenectomy. Laparoscopic splenectomy was associated with higher risk of VTE than open splenectomy. 97% of patients were prescribed prophylactic antibiotics on discharge, but only 88% had received recommended vaccinations. Conclusion: Venous thromboembolism is common post splenectomy. Our data showed that BMI ≥30 was associated with a statistically significant increased risk of VTE, while the use of prophylactic anticoagulation was associated with reduced risk. Further prospective studies with larger samples are warranted and a splenectomy care plan may be helpful.