• Identification of Distinct Long COVID Clinical Phenotypes Through Cluster Analysis of Self-Reported Symptoms.

      Kenny, Grace; McCann, Kathleen; O'Brien, Conor; Savinelli, Stefano; Tinago, Willard; Yousif, Obada; Lambert, John S; O'Broin, Cathal; Feeney, Eoin R; de Barra, Eoghan; et al. (2022-03-07)
      Abstract Background: We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID. Methods: This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters. Results: Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range [IQR], 36-54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 [IQR, 2-3] symptoms per individual in cluster 3 vs 6 [IQR, 5-7] and 4 [IQR, 3-5] in clusters 1 and 2, respectively; P < .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning. Conclusions: Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.
    • STOP-HF Trial: Higher Endogenous BNP and Cardiovascular Protection in Subjects at Risk for Heart Failure.

      Cannone, Valentina; Ledwidge, Mark; Watson, Chris; McKie, Paul M; Burnett, John C; McDonald, Kenneth (2021-06-16)
      B-type natriuretic peptide (BNP) possesses blood-pressure-lowering, antifibrotic, and aldosterone-suppressing properties. In Stage A and B heart failure, the carriers of the minor C allele of the BNP genetic variant rs198389 have higher circulating levels of BNP and are at decreased risk of hypertension, new-onset left ventricular systolic dysfunction, and hospitalization for major adverse cardiovascular events. Future studies are warranted to investigate the role of BNP genetic testing and BNP-based therapy in the prevention of heart failure. Keywords: B-type natriuretic peptide; BNP, B-type natriuretic peptide; HF, heart failure; LVSD, left ventricular systolic dysfunction; RAAS, renin-angiotensin-aldosterone system; SNP, single nucleotide polymorphism; STOP-HF Trial; heart failure; pGC-A, particulate guanylyl cyclase A receptor; rs198389; single nucleotide polymorphism.
    • 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.
    • A national survey of publicly funded chronic pain management services in Ireland.

      Purcell, Andrew; Channappa, Keshava; Moore, David; Harmon, Dominic (2021-06-10)
      Background: Chronic pain management services have historically been under-resourced in Ireland. There is no agreed model of care for chronic pain management services in Ireland. Previous studies have assessed the extent of services in Ireland without examining waiting times for access to services. Aims: This study aimed to quantify the extent of, geographical distribution of and waiting times for access to publicly funded chronic pain management services in Ireland. Methods: Using the British Pain Society's Core Standards for Pain Management Services in the UK (2015) and International Association for the Study of Pain (IASP) recommendations, a questionnaire was devised. Publically funded departments in Ireland were contacted and questionnaires completed. Waiting list data was publicly available and obtained from the National Treatment Purchase Fund website. Results: There was a 100% response rate. Sixteen publicly funded chronic pain management services were identified. There are 27 chronic pain management consultants (16.6 whole time equivalents (WTE)) practicing chronic pain management, amounting to 0.55 specialists (0.34 WTEs)/100,000 of the population. There are 21 WTE for non-consultant hospital doctors (NCHDs), 26.5 WTEs for nursing, 8 WTEs for physiotherapy and 6.2 WTEs for psychology, nationally. A percentage of 93.75% of departments (n = 15) provide interventional therapies, 37.5% (n = 6) provide advanced neuromodulation and 43.75% (n = 7) are managing intrathecal pump therapies. There are five pain management programmes nationally. As of January 2020, ~ 25% patients on waiting lists for outpatient appointments were waiting > 18 months, with ~ 17% patients on waiting lists for interventional treatments waiting > 12 months. Conclusions: Shortage of multidisciplinary staff is of particular concern for Irish services. Patient access is limited as evidenced by significant waiting lists. In order to improve access to care and bring services in line with international recommendations, increased resources are needed.
    • Intraoperative Monitoring of the Obese Patient Undergoing Surgery: A Narrative Review.

      Haren, Andrea P; Nair, Shrijit; Pace, Maria C; Sansone, Pasquale (2021-06-05)
      With the increasing prevalence of obesity in the population, anaesthetists must confidently manage both the pathophysiological and technical challenges presented in bariatric and non-bariatric surgery. The intraoperative period represents an important opportunity to optimise and mitigate risk. However, there is little formal guidance on what intraoperative monitoring techniques should be used in this population. This narrative review collates the existing evidence for intraoperative monitoring devices in the obese patients. Although a number of non-invasive blood pressure monitors have been tested, an invasive arterial line remains the most reliable monitor if accurate, continuous monitoring is required. Goal-directed fluid therapy is recommended by clinical practice guidelines, but the methods tested to assess this had guarded applicability to the obese population. Transcutaneous carbon dioxide (CO2) monitoring may offer additional benefit to standard capnography in this population. Individually titrated positive end expiratory pressure (PEEP) and recruitment manoeuvres improved intraoperative mechanics but yielded no benefit in the immediate postoperative period. Depth of anaesthesia monitoring appears to be beneficial in the perioperative period regarding recovery times and complications. Objective confirmation of reversal of neuromuscular blockade continues to be a central tenet of anaesthesia practice, particularly relevant to this group who have been characterised as an "at risk" extubation group. Where deep neuromuscular blockade is used, continuous neuromuscular blockade is suggested. Both obesity and the intraoperative context represent somewhat unstable search terms, as the clinical implications of the obesity phenotype are not uniform, and the type and urgency of surgery have significant impact on the intraoperative setting. This renders the generation of summary conclusions around what intraoperative monitoring techniques are suitable in this population highly challenging.
    • Dystonia Management: What to Expect From the Future? The Perspectives of Patients and Clinicians Within DystoniaNet Europe.

      Smit, Marenka; Albanese, Alberto; Benson, Monika; Edwards, Mark J; Graessner, Holm; Hutchinson, Michael; Jech, Robert; Krauss, Joachim K; Morgante, Francesca; Pérez Dueñas, Belen; et al. (2021-06-03)
      Improved care for people with dystonia presents a number of challenges. Major gaps in knowledge exist with regard to how to optimize the diagnostic process, how to leverage discoveries in pathophysiology into biomarkers, and how to develop an evidence base for current and novel treatments. These challenges are made greater by the realization of the wide spectrum of symptoms and difficulties faced by people with dystonia, which go well-beyond motor symptoms. A network of clinicians, scientists, and patients could provide resources to facilitate information exchange at different levels, share mutual experiences, and support each other's innovative projects. In the past, collaborative initiatives have been launched, including the American Dystonia Coalition, the European Cooperation in Science and Technology (COST-which however only existed for a limited time), and the Dutch DystonieNet project. The European Reference Network on Rare Neurological Diseases includes dystonia among other rare conditions affecting the central nervous system in a dedicated stream. Currently, we aim to broaden the scope of these initiatives to a comprehensive European level by further expanding the DystoniaNet network, in close collaboration with the ERN-RND. In line with the ERN-RND, the mission of DystoniaNet Europe is to improve care and quality of life for people with dystonia by, among other endeavors, facilitating access to specialized care, overcoming the disparity in education of medical professionals, and serving as a solid platform to foster international clinical and research collaborations. In this review, both professionals within the dystonia field and patients and caregivers representing Dystonia Europe highlight important unsolved issues and promising new strategies and the role that a European network can play in activating them.
    • Changing attitudes towards annual influenza vaccination amongst staff in a Tertiary Care Irish University Hospital.

      Kearns, Emma C; Callanan, Ian; O'Reilly, Ann; Purcell, Aisling; Tuohy, Niamh; Bulfin, Siobhan; Smyth, Angela; Bairead, Emer; Fitzgerald, Susan; Feeney, Eoin; et al. (2021-05-13)
      Background: Healthcare workers are encouraged annually to get vaccinated against influenza. This year in view of COVID-19 pandemic, attitudes of HCWs towards vaccination are particularly important. A cross-sectional study was completed to understand how to best encourage and facilitate the vaccination of HCWs based on the previous years' findings. Methods: An online survey was disseminated to all hospital staff via electronic channels. The clinical audit sphinx software was used for data collection and analysis. Results: The total number of responses was n = 728, almost double the rate from 2018 (N = 393). A total of 78% (N = 551) of participants were vaccinated last year. A total of 94% (N = 677) of participants reported their intention to be vaccinated this year. The main barriers listed were being unable to find time (32%, N = 36), side effects (30%, N = 33) and thinking that it does not work (21%, N = 23). The most popular suggestions for how to increase uptake were more mobile immunisation clinics (72%, N = 517) and more information on the vaccine (50%, N = 360). A total of 82% of participants (N = 590) agreed that healthcare workers should be vaccinated, with 56% (N = 405) agreeing that it should be mandatory. Of the participants who were not vaccinated last year (N = 159), 40% (N = 63) agreed that COVID-19 had changed their opinion on influenza immunisation with a further 11% (N = 18) strongly agreeing. Discussion: In light of the increasing number of survey participants, more staff were interested in flu vaccination this year than ever before. The COVID-19 pandemic has had some influence on staff's likelihood to be vaccinated. Feasibility of immunisation and education posed the largest barriers to HCW vaccination.
    • Should denosumab treatment for osteoporosis be continued indefinitely?

      Noble, Jane A; McKenna, Malachi J; Crowley, Rachel K (2021-04-22)
      Denosumab was approved for the treatment of postmenopausal osteoporosis in 2010, based on the FREEDOM study, which indicated a benefit in terms of increased bone mineral density and reduced risk of major osteoporotic fracture. In the initial clinical studies it was noted that discontinuation of denosumab can lead to a rebound of bone turnover markers and loss of accrued bone mineral density. An increased risk of fractures (multiple vertebral fractures in particular) associated with discontinuation was noted after approval and marketing of denosumab. For many patients experiencing gain in bone mineral density and fracture prevention while taking denosumab, there is no reason to stop therapy. However, discontinuation of denosumab may happen due to non-adherence; potential lack of efficacy in an individual; where reimbursement for therapy is limited to those with bone mineral density in the osteoporosis range, when assessment reveals this has been exceeded; or patient or physician concern regarding side effects. This review paper aims to discuss these concerns and to summarize the data available to date regarding sequential osteoporosis therapy following denosumab cessation to reduce the risk of multiple vertebral fracture.
    • Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

      Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; et al. (2021-04-15)
      Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
    • Exosomes: a new perspective in EGFR-mutated lung cancer.

      Jouida, Amina; McCarthy, Cormac; Fabre, Aurelie; Keane, Michael P (2021-04-14)
      Exosomes are major contributors in cell to cell communication due to their ability to transfer biological material such as protein, RNA, DNA, and miRNA. Additionally, they play a role in tumor initiation, promotion, and progression, and recently, they have emerged as a potential source of information on tumor detection and may be useful as diagnostic, prognostic, and predictive tools. This review focuses on exosomes from lung cancer with a focus on EGFR mutations. Here, we outline the role of exosomes and their functional effect in carcinogenesis, tumor progression, and metastasis. Finally, we discuss the possibility of exosomes as novel biomarkers in early detection, diagnosis, assessment of prognosis, and prediction of therapeutic response in EGFR-mutated lung cancer.
    • Colonisation of the colonic mucus gel layer with butyrogenic and hydrogenotropic bacteria in health and ulcerative colitis.

      Earley, Helen; Lennon, Grainne; Coffey, J Calvin; Winter, Desmond C; O'Connell, P Ronan (2021-03-31)
      Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others may inhibit butyrate, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL). Mucosal brushings were obtained from 20 healthy controls (HC), 20 patients with active colitis (AC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann-Whitney-U and Kruskall-Wallis tests. Butyrogenic R. hominis was more abundant in health than UC (p < 0.005), prior to normalisation against total bacteria. Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p < 0.005). An inverse correlation existed between inflammation and R. hominis (ρ - 0.460, p < 0.005) and B. wadsworthia (ρ - 0.646, p < 0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.
    • Dynamic Change and Clinical Relevance of Postinfectious SARS-CoV-2 Antibody Responses.

      Mallon, Patrick; Tinago, Willard; Leon, Alejandro Garcia; McCann, Kathleen; Kenny, Grace; McGettrick, Padraig; Green, Sandra; Inzitari, Rosanna; Cottere, Aoife G; Feeney, Eoin R; et al. (2021-03-26)
      Background: Although reports suggest that most individuals with coronavirus disease 2019 (COVID-19) develop detectable antibodies postinfection, the kinetics, durability, and relative differences between immunoglobulin M (IgM) and immunoglobulin G (IgG) responses beyond the first few weeks after symptom onset remain poorly understood. Methods: Within a large, well-phenotyped, diverse, prospective cohort of subjects with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity, specificity, and relationship with disease severity and mapped the kinetics of antibody responses over time using generalized additive models. Results: We analyzed 1001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1%-47.1%) early (<10 days) after symptom onset but increased to >80% after 10 days. IgM positivity increased earlier than IgG-targeted assays, but positivity peaked between days 32 and 38 post-onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analyzed, with a more rapid decline observed with IgM. Early (<10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal/cutoff 4.20 [0.75-17.93] vs 1.07 [0.21-5.46]; P = .048). Conclusions: This study suggests that postinfectious antibody responses in those with confirmed COVID-19 begin to decline relatively early postinfection and suggests a potential role for higher IgM levels early in infection in the prediction of subsequent disease severity.
    • Real‑world challenge for clinicians treating advanced gastroesophageal adenocarcinoma (Review).

      Baxter, Mark A; Petty, Russell D; Swinson, Daniel; Hall, Peter S; O'Hanlon, Shane (2021-03-24)
      Gastroesophageal adenocarcinoma (GOA) is a disease of older people. Incidence is rising in the developed world and the majority of patients present with advanced disease. Based on clinical trial data, systemic chemotherapy in the advanced setting is associated with improvements in quality of life and survival. However, there is a recognised mismatch between trial populations and the patients encountered in clinical practice in terms of age, comorbidity and fitness. Appropriate patient selection is essential to safely deliver effective treatment. In this narrative review, we discuss the challenges faced by clinicians when assessing real‑world patients with advanced GOA for systemic therapy. We also highlight the importance of frailty screening and the current available evidence we can use to guide our management.
    • 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).
    • 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.
    • Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer.

      Katayama, Ayaka; Miligy, Islam M; Shiino, Sho; Toss, Michael S; Eldib, Karim; Kurozumi, Sasagu; Quinn, Cecily M; Badr, Nahla; Murray, Ciara; Provenzano, Elena; et al. (2021-02-01)
      The response of human epidermal growth factor receptor2 (HER2)- positive breast cancer (BC) patients to anti-HER2 targeted therapy is significant. However, the response is not uniform and a proportion of HER2-positive patients do not respond. This study aims to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive BC patients. The study group comprised 500 BC patients treated with neoadjuvant chemotherapy (NACT) and/or neoadjuvant anti-HER2 therapy and surgery who had tumours that were 3+ or 2+ with HER2 immunohistochemistry (IHC). HER2 IHC 2+ tumours were classified into five groups by fluorescence in situ hybridisation (FISH) according to the 2018 ASCO/CAP guidelines of which Groups 1, 2 and 3 were considered HER2 amplified. Pathological complete response (pCR) was more frequent in HER2 IHC 3+ tumours than in HER2 IHC 2+/HER2 amplified tumours, when either in receipt of NACT alone (38% versus 13%; p = 0.22) or neoadjuvant anti-HER2 therapy (52% versus 20%; p < 0.001). Multivariate logistic regression analysis showed that HER2 IHC 3+ and histological grade 3 were independent predictors of pCR following neoadjuvant anti-HER2 therapy. In the HER2 IHC 2+/HER2 amplified tumours or ASCO/CAP FISH Group 1 alone, ER-negativity was an independent predictor of pCR following NACT and/or neoadjuvant anti-HER2 therapy. In the current study, 22% of HER2-positive tumours became HER2-negative by IHC and FISH following neoadjuvant treatment, the majority (74%) HER2 IHC 2+/HER2 amplified tumours. Repeat HER2 testing after neoadjuvant treatment should therefore be considered.
    • Family-related non-abuse adverse life experiences occurring for adults diagnosed with eating disorders: a systematic review.

      Grogan, Katie; MacGarry, Diarmuid; Bramham, Jessica; Scriven, Mary; Maher, Caroline; Fitzgerald, Amanda (2020-07-22)
      Background: Although previous reviews suggest a strong association between abuse and eating disorders, less is known about non-abuse adverse life experiences, such as parental mental illness or family discord, which occur frequently for this population. The aim of the current study was to identify family-related non-abuse adverse life experiences occurring for adults with eating disorders, and to establish whether they occur for people with anorexia nervosa, bulimia nervosa or binge-eating disorder more than the general population and other psychiatric populations. Method: A systematic review of studies focusing on family-related non-abuse adverse life experiences and eating disorders was conducted in accordance with PRISMA guidelines. The search string was applied to four electronic databases including Psycinfo, PubMed/Medline, CINAHL Plus and EMBASE. Results: Of the 26 studies selected for inclusion, six types of family-related non-abuse adverse life experiences were identified: adverse parenting style; family disharmony; loss of a family member, relative or close person; familial mental health issues; family comments about eating, or shape, weight and appearance; and family disruptions. Findings provided tentative evidence for eating disorder specific (i.e. parental demands and criticism) and non-specific (i.e. familial loss and family disruptions) non-abuse adversities, with findings also suggesting that those with bulimia nervosa and binge-eating disorder were more impacted by loss, family separations and negative parent-child interactions compared to those with anorexia nervosa. Conclusions: This review provides a clear synthesis of previous findings relating to family-related non-abuse adverse life experiences and eating disorders in adults. Implications for trauma-informed care in clinical practice were discussed (e.g. considering the impact of past life events, understanding the function of ED behaviours, reducing the risk of potential re-traumatisation).
    • Correction to: Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

      Rieckmann, Nina; Neumann, Konrad; Feger, Sarah; Ibes, Paolo; Napp, Adriane; Preuß, Daniel; Dreger, Henryk; Feuchtner, Gudrun; Plank, Fabian; Suchánek, Vojtěch; et al. (2020-06-29)
    • Developing a lung nodule management protocol specifically for cardiac CT: Methodology in the DISCHARGE trial.

      Haase, Robert; Dodd, Jonathan D; Kauczor, Hans-Ulrich; Kazerooni, Ella A; Dewey, Marc (2020-06-25)
      Purpose: In this methodology paper we describe the development of a lung nodule management algorithm specifically for patients undergoing cardiac CT. Methods: We modified the Lung-RADS algorithm specifically to manage lung nodules incidentally detected on cardiac CT (Lung-RADS for cardiac CT). We will evaluate the modified algorithm as part of the DISCHARGE trial (www.dischargetrial.eu) in which patients with suspected coronary artery disease are randomly assigned to cardiac CT or invasive coronary angiography across Europe at 16 sites involving 3546 patients. Patients will be followed for up to four years. Results: The major adjustments to Lung-RADS specifically for cardiac CT relate to 1) incomplete coverage of the lungs by cardiac CT compared with chest CT, and when to order a completion chest CT versus a follow up chest CT, 2) cardiac CT findings will not trigger annual lung-cancer screening, and 3) a lower threshold of at least 10 mm for classifying new ground glass nodules as probably benign (category 3). Conclusions: The DISCHARGE trial will assess a lung nodule management algorithm designed specifically for cardiac CT in patients with stable chest pain across Europe.
    • Development and use of health outcome descriptors: a guideline development case study.

      Baldeh, Tejan; Saz-Parkinson, Zuleika; Muti, Paola; Santesso, Nancy; Morgano, Gian Paolo; Wiercioch, Wojtek; Nieuwlaat, Robby; Gräwingholt, Axel; Broeders, Mireille; Duffy, Stephen; et al. (2020-06-05)
      Background: During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed 'health outcome descriptors' for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers. Methods: We developed 24 health outcome descriptors related to breast cancer screening and diagnosis for the European Commission Breast Guideline Development Group (GDG). Eighteen GDG members provided feedback in written format or in interviews. We then evaluated the process and conducted two health utility rating surveys. Results: Feedback from GDG members revealed that health outcome descriptors are probably useful for developing recommendations and improving transparency of guideline methods. Time commitment, methodology training, and need for multidisciplinary expertise throughout development were considered important determinants of the process. Comparison of the two health utility surveys showed a decrease in standard deviation in the second survey across 21 (88%) of the outcomes. Conclusions: Health outcome descriptors are feasible and should be developed prior to the outcome prioritization step in the guideline development process. Guideline developers should involve a subgroup of multidisciplinary experts in all stages of development and ensure all guideline panel members are trained in guideline methodology that includes understanding the importance of defining and understanding the outcomes of interest.