• PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer.

      van den Heerik, Anne Sophie V M; Horeweg, Nanda; Nout, Remi A; Lutgens, Ludy C H W; van der Steen-Banasik, Elzbieta M; Westerveld, G Henrike; van den Berg, Hetty A; Slot, Annerie; Koppe, Friederike L A; Kommoss, Stefan; et al. (2020-10-12)
      Background: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. Primary objectives: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. Trial design: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). Major inclusion/exclusion criteria: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). Endpoints: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. Sample size: 500 eligible and evaluable patients. Estimated dates for completing accrual and presenting results: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. Trial registration: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025). Keywords: endometrium; radiation oncology.
    • Involving Clients to Inform Development and Implementation of Combined Type 2 Diabetes and Chronic Kidney Disease Care Using Discovery Interview Technique.

      Blanchfield, Denise; O'Connor, Laserina (Innovational Publishers, 2020-10)
      The development of chronic kidney disease in persons with Type 2 diabetes has been described as an epidemic. Standard outpatient care for these associated conditions is routinely provided separately, resulting in missed opportunities to implement preventative and early management strategies. Historically, care delivery for these combined conditions has fallen within the remit of medical professionals, evidenced by a dearth of information pertaining to the contribution of advanced practice nursing for this cohort. Clients report an uncoordinated impersonal approach to care delivery for associated conditions, however incorporating their experience is vital to the delivery of patient centered care and will be included in this study through their stories. The primary aim of this participatory action research (PAR) study is to utilize the client care stories and health-care professional perspectives to inform development and implementation of a new combined Type 2 diabetes and chronic kidney disease service in the context of advanced practice nursing. Methodology: This study adopted a PAR approach informed by patient discovery interviews and key stakeholders focus groups. Transcripts will be developed from discovery interviews and focus groups and analyzed using thematic analysis. Results: The PAR will utilize thematic analysis outcomes to inform the primary aim and clinical outcomes from combined care will be evaluated after 9 months by retrospective chart review. Conclusion: The approach adopted in this study represents a departure from traditional medically led care strategies. Outcomes may elucidate potential challenges to the development and delivery of innovative care delivery for underserved patient cohorts in the context of advanced practice nursing.
    • Accuracy of the clinical pulmonary infection score to differentiate ventilator-associated tracheobronchitis from ventilator-associated pneumonia.

      Gaudet, Alexandre; Martin-Loeches, Ignacio; Povoa, Pedro; Rodriguez, Alejandro; Salluh, Jorge; Duhamel, Alain; Nseir, Saad (2020-08-03)
      Background: Differentiating Ventilator-Associated Tracheobronchitis (VAT) from Ventilator-Associated Pneumonia (VAP) may be challenging for clinicians, yet their management currently differs. In this study, we evaluated the accuracy of the Clinical Pulmonary Infection Score (CPIS) to differentiate VAT and VAP. Methods: We performed a retrospective analysis based on the data from 2 independent prospective cohorts. Patients of the TAVeM database with a diagnosis of VAT (n = 320) or VAP (n = 369) were included in the derivation cohort. Patients admitted to the Intensive Care Centre of Lille University Hospital between January 1, 2016 and December 31, 2017 who had a diagnosis of VAT (n = 70) or VAP (n = 139) were included in the validation cohort. The accuracy of the CPIS to differentiate VAT from VAP was assessed within the 2 cohorts by calculating sensitivity and specificity values, establishing the ROC curves and choosing the best threshold according to the Youden index. Results: The areas under ROC curves of CPIS to differentiate VAT from VAP were calculated at 0.76 (95% CI [0.72-0.79]) in the derivation cohort and 0.67 (95% CI [0.6-0.75]) in the validation cohort. A CPIS value ≥ 7 was associated with the highest Youden index in both cohorts. With this cut-off, sensitivity and specificity were respectively found at 0.51 and 0.88 in the derivation cohort, and at 0.45 and 0.89 in the validation cohort. Conclusions: A CPIS value ≥ 7 reproducibly allowed to differentiate VAT from VAP with high specificity and PPV and moderate sensitivity and NPV in our derivation and validation cohorts.
    • Social isolation due to the COVID-19 pandemic has led to worse outcomes in females with inflammatory arthritis.

      Maguire, Sinead; O'Shea, Finbar (2020-07-12)
      Background: Prolonged social isolation as a result of the COVID-19 global pandemic has been a source of considerable psychological distress for many people. This can manifest in many ways and if left undetected can impact negatively on general health. It is essential to understand the impact of these conditions on inflammatory arthritis (IA) patients, especially axial spondyloarthropathy (axSpA). Aim: To capture the level of psychological distress for patients with IA following prolonged social isolation. Methods: A survey was sent out to patients with a confirmed diagnosis of IA. This captured changes in sleep, mood, disease activity, employment and general health since the beginning of the social isolation period. A PHQ-4 (Patient Health Questionnaire) was included to determine level of psychological distress. Results: Females with IA reported significantly higher rates of decline in general health (40% vs 16%, p = 0.01), mood disturbance (43.4% vs 26%, p = 0.03) and increased disease activity (50% vs 16%, p = 0.01) compared to males. Evaluating the mean PHQ-4 scores, no significant difference was noted between genders (4.80 vs 3.44, p = 0.10). However, females demonstrated a non-significant trend toward increased rates of moderate to severe psychological distress (40% vs 30%, p = 0.13). Subanalysis of patients with axSpA found high rates of moderate to severe distress in both genders. Conclusions: Females with IA reported significantly higher rates of decline in general health, mood disturbance and increased disease activity during the period of social isolation. This was reflected in a trend towards greater levels of psychological distress.
    • The development and cognitive testing of the positive outcomes HIV PROM: a brief novel patient-reported outcome measure for adults living with HIV.

      Bristowe, K; Murtagh, F E M; Clift, P; James, R; Josh, J; Platt, M; Whetham, J; Nixon, E; Post, F A; McQuillan, K; et al. (2020-07-06)
      Background: People living with HIV experience burdensome multidimensional symptoms and concerns requiring person-centred care. Routine use of patient reported outcome measures can improve outcomes. There is no brief patient reported outcome measure (PROM) that currently reflects the breadth of concerns for people living with HIV. This study aimed to develop and cognitively test a brief novel patient reported outcome measure for use within routine adult HIV care- the "Positive Outcomes" HIV PROM. Methods: Development followed the COSMIN taxonomy and guidance for relevance and comprehensiveness, and Rothrock guidance on development of valid patient reported outcome measures. The Positive Outcomes HIV PROM was developed by a steering group (people living with HIV, HIV professionals and health services researchers) using findings from a previously reported qualitative study of priority outcomes for people living with HIV. The prototype measure was cognitively tested with a purposive sample of people living with HIV. Results: The Positive Outcomes HIV PROM consists of 23 questions (22 structured, and one open question) informed by the priorities of key stakeholders (n = 28 people living with HIV, n = 21 HIV professionals and n = 8 HIV commissioners) to ensure face and content validity, and refined through cognitive testing (n = 6 people living with HIV). Cognitive testing demonstrated high levels of acceptability and accessibility. Conclusions: The Positive Outcomes HIV PROM is the first brief patient reported outcome measure reflecting the diverse needs of people living with HIV designed specifically for use in the clinical setting to support patient assessment and care, and drive service quality improvement. It is derived from primary data on the priority outcomes for people living with HIV and is comprehensive and acceptable. Further psychometric testing is required to ensure reliability and responsiveness.
    • Recommendations for core critical care ultrasound competencies as a part of specialist training in multidisciplinary intensive care: a framework proposed by the European Society of Intensive Care Medicine (ESICM).

      Wong, Adrian; Galarza, Laura; Forni, Lui; De Backer, Daniel; Slama, Michael; Cholley, Bernard; Mayo, Paul; McLean, Anthony; Vieillard-Baron, Antoine; Lichtenstein, Daniel; et al. (2020-07-03)
      Critical care ultrasound (CCUS) is an essential component of intensive care practice. Although existing international guidelines have focused on training principles and determining competency in CCUS, few countries have managed to operationalize this guidance into an accessible, well-structured programme for clinicians training in multidisciplinary intensive care. We seek to update and reaffirm appropriate CCUS scope so that it may be integrated into the international Competency-based Training in Intensive Care Medicine. The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described. Importantly, we discuss the rationale for inclusion but also exclusion of competencies listed. Background/aim: Critical care ultrasound (CCUS) is an essential component of intensive care practice. The purpose of this consensus document is to determine those CCUS competencies that should be a mandatory part of training in multidisciplinary intensive care. Methods: A three-round Delphi method followed by face-to-face meeting among 32 CCUS experts nominated by the European Society of Intensive Care Medicine. Agreement of at least 90% of experts was needed in order to enlist a competency as mandatory. Results: The final list of competencies includes 15 echocardiographic, 5 thoracic, 4 abdominal, deep vein thrombosis diagnosis and central venous access aid. Conclusion: The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described.
    • Youth mental health in the time of COVID-19.

      Power, Emmet; Hughes, S; Cotter, D; Cannon, M (2020-07-02)
      Youth mental health is a rapidly developing field with a focus on prevention, early identification, treatment innovation and service development. In this perspective piece, we discuss the effects of COVID-19 on young people's mental health. The psychosocial effects of COVID-19 disproportionately affect young people. Both immediate and longer-term factors through which young people are affected include social isolation, changes to the delivery of therapeutic services and almost complete loss of all structured occupations (school, work and training) within this population group. Longer-term mechanisms include the effects of the predicted recession on young people's mental health. Opportunities within this crisis exist for service providers to scale up telehealth and digital services that may benefit service provision for young people's mental health in the future.
    • Linezolid resistance in Enterococcus faecium and Enterococcus faecalis from hospitalized patients in Ireland: high prevalence of the MDR genes optrA and poxtA in isolates with diverse genetic backgrounds.

      Egan, Sarah A; Shore, Anna C; O'Connell, Brian; Brennan, Grainne I; Coleman, David C (2020-07)
      Objectives: To investigate the prevalence of the optrA, poxtA and cfr linezolid resistance genes in linezolid-resistant enterococci from Irish hospitals and to characterize associated plasmids. Methods: One hundred and fifty-four linezolid-resistant isolates recovered in 14 hospitals between June 2016 and August 2019 were screened for resistance genes by PCR. All isolates harbouring resistance genes, and 20 without, underwent Illumina MiSeq WGS. Isolate relatedness was assessed using enterococcal whole-genome MLST. MinION sequencing (Oxford Nanopore) and hybrid assembly were used to resolve genetic environments/plasmids surrounding resistance genes. Results: optrA and/or poxtA were identified in 35/154 (22.7%) isolates, the highest prevalence reported to date. Fifteen isolates with diverse STs harboured optrA only; one Enterococcus faecium isolate harboured optrA (chromosome) and poxtA (plasmid). Seven Enterococcus faecalis and one E. faecium harboured optrA on a 36 331 bp plasmid with 100% identity to the previously described optrA-encoding conjugative plasmid pE349. Variations around optrA were also observed, with optrA located on plasmids in five isolates and within the chromosome in three isolates. Nine E. faecium and 10 E. faecalis harboured poxtA, flanked by IS1216E, within an identical 4001 bp region on plasmids exhibiting 72.9%-100% sequence coverage to a 21 849 bp conjugative plasmid. E. faecalis isolates belonged to ST480, whereas E. faecium isolates belonged to diverse STs. Of the remaining 119 linezolid-resistant isolates without linezolid resistance genes, 20 investigated representatives all harboured the G2576T 23S RNA gene mutation associated with linezolid resistance. Conclusions: This high prevalence of optrA and poxtA in diverse enterococcal lineages in Irish hospitals indicates significant selective pressure(s) for maintenance.
    • 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)
    • Update of the treatment of nosocomial pneumonia in the ICU.

      Zaragoza, Rafael; Vidal-Cortés, Pablo; Aguilar, Gerardo; Borges, Marcio; Diaz, Emili; Ferrer, Ricard; Maseda, Emilio; Nieto, Mercedes; Nuvials, Francisco Xavier; Ramirez, Paula; et al. (2020-06-29)
      In accordance with the recommendations of, amongst others, the Surviving Sepsis Campaign and the recently published European treatment guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), in the event of a patient with such infections, empirical antibiotic treatment must be appropriate and administered as early as possible. The aim of this manuscript is to update treatment protocols by reviewing recently published studies on the treatment of nosocomial pneumonia in the critically ill patients that require invasive respiratory support and patients with HAP from hospital wards that require invasive mechanical ventilation. An interdisciplinary group of experts, comprising specialists in anaesthesia and resuscitation and in intensive care medicine, updated the epidemiology and antimicrobial resistance and established clinical management priorities based on patients' risk factors. Implementation of rapid diagnostic microbiological techniques available and the new antibiotics recently added to the therapeutic arsenal has been reviewed and updated. After analysis of the categories outlined, some recommendations were suggested, and an algorithm to update empirical and targeted treatment in critically ill patients has also been designed. These aspects are key to improve VAP outcomes because of the severity of patients and possible acquisition of multidrug-resistant organisms (MDROs).
    • Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion.

      Verweij, Paul E; Rijnders, Bart J A; Brüggemann, Roger J M; Azoulay, Elie; Bassetti, Matteo; Blot, Stijn; Calandra, Thierry; Clancy, Cornelius J; Cornely, Oliver A; Chiller, Tom; et al. (2020-06-22)
      Purpose: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. Methods: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Results: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. Conclusion: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.
    • A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases.

      Xu, Jing; Higgins, Michaela J; Tolaney, Sara M; Come, Steven E; Smith, Matthew R; Fornier, Monica; Mahmood, Umar; Baselga, Jose; Yeap, Beow Y; Chabner, Bruce A; et al. (2020-06-18)
      Background: We assessed the antitumor activity of cabozantinib, a potent multireceptor oral tyrosine kinase inhibitor, in patients with hormone receptor-positive breast cancer with bone metastases. Patients and methods: In this single-arm multicenter phase II study, patients received an initial starting dose of 100 mg, later reduced to 60 mg, per day. The primary endpoint was the bone scan response rate. Secondary endpoints included objective response rate by RECIST, progression-free survival (PFS), and overall survival (OS). Results: Of 52 women enrolled, 20 (38%) experienced a partial response on bone scan and 6 (12%) had stable disease. Prior to the first repeat bone scan at 12 weeks, 19 (35%) patients discontinued study treatment because of early clinical progression or unacceptable toxicity. RECIST evaluation based on best overall response by computed tomography revealed stable disease in extraosseous tissues in 26 patients (50%) but no complete or partial responses. In 25 patients with disease control on bone scan at 12 weeks, only 3 (12%) patients developed extraosseous progression. The median PFS was 4.3 months, and median OS was 19.6 months. The most common grade 3 or 4 toxicities were hypertension (10%), anorexia (6%), diarrhea (6%), fatigue (4%), and hypophosphatemia (4%). Conclusion: Bone scans improved in 38% of patients with metastatic hormone receptor-positive breast cancer and remained stable in an additional 12% for a minimum duration of 12 weeks on cabozantinib. Further investigations should assess the activity of cabozantinib in combination with other hormonal and other breast cancer therapies and determine whether bone scan responses correlate with meaningful antitumor effects. ClinicalTrials.gov identifier. NCT01441947 IMPLICATIONS FOR PRACTICE: Most patients with metastatic hormone receptor-positive (HR+) breast cancer have bone involvement, and many have bone-only disease, which is difficult to evaluate for response. This phase II single-arm study evaluated the clinical activity of the small molecule MET/RET/VEGFR2 inhibitor cabozantinib in patients with metastatic HR+ breast cancer with bone metastases. This study met its primary endpoint, and cabozantinib treatment resulted in a significant bone scan response rate correlating with improved survival. This is the first study to use bone scan response as a primary endpoint in breast cancer. The results support further study of cabozantinib in HR+ breast cancer.
    • Down syndrome and oral health: mothers' perception on their children's oral health and its impact.

      AlJameel, AlBandary H; Watt, Richard G; Tsakos, Georgios; Daly, Blánaid (2020-06-16)
      Background: Individuals with Down syndrome exhibit particular oro-facial characteristics that may increase their risk of oral health problems. However, there is little research on the oral health of children and adults with Down syndrome and the way that oral health may affect Quality of Life (QoL). This study explored mothers' perceptions of the oral health problems experienced by their children with Down syndrome and how these reported problems impacted the lives of the children and their families. Methods: The study involved 20 in-depth, semi-structured interviews with mothers of children and adolescents aged 12-18 years with Down syndrome attending special care centres in Riyadh, Saudi Arabia. Results: The predominant oral-health related problem reported by mothers was difficulty in speaking. Mothers also reported that tooth decay and toothache were problems that had undesirable effects on different aspects of their children's QoL including: performing daily activities, emotional wellbeing, and social relationships. Poor oral health and functional problems had direct and indirect impacts on the family's QoL as well. Conclusion: Mothers perceived an array of QoL impacts from oral conditions, which affected their child with Down syndrome and the wider family.
    • COVID-19 and Congenital Heart Disease: Results from a Nationwide Survey.

      Sabatino, Jolanda; Ferrero, Paolo; Chessa, Massimo; Bianco, Francesco; Ciliberti, Paolo; Secinaro, Aurelio; Oreto, Lilia; Avesani, Martina; Bucciarelli, Valentina; Calcaterra, Giuseppe; et al. (2020-06-08)
      This is a multi-centre, observational, nationwide survey, involving high-volume Italian CHD centres. COVID-19 diagnosis was defined as either "clinically suspected" or "confirmed", where a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) test had been performed and was positive. Cardiovascular comorbidities were observed among adult patients-atrial fibrillation (seven; 9%), hypertension (five; 7%), obesity (seven; 9%) and diabetes (one; 1%)-but were absent among children. Cardiovascular complications were mainly observed in the "confirmed" COVID-19+ group, consisting of heart failure (9%), palpitations/arrhythmias (3%), stroke/TIA (3%) and pulmonary hypertension (3%). Cardiovascular symptoms such as chest pain (1%), myocardial injury (1%) and pericardial effusion (1%) were also recorded. On the contrary, CHD patients from the clinically suspected COVID-19 group presented no severe symptoms or complications.
    • 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.
    • EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update.

      Gossec, Laure; Baraliakos, Xenofon; Kerschbaumer, Andreas; de Wit, Maarten; McInnes, Iain; Dougados, Maxime; Primdahl, Jette; McGonagle, Dennis G; Aletaha, Daniel; Balanescu, Andra; et al. (2020-06)
      Objective: To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA). Methods: According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined. Results: The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed. Conclusion: These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.
    • Dendritic Cell-Based Therapy Using LY6E Peptide with a Putative Role Against Colorectal Cancer.

      Tokhanbigli, Samaneh; Asadirad, Ali; Baghaei, Kaveh; Piccin, Andrea; Yarian, Fatemeh; Parsamanesh, Gilda; Hashemi, Seyed Mahmoud; Asadzadeh Aghdaei, Hamid; Zali, Mohammad Reza (2020-05-22)
      Introduction: Albeit early stage gastrointestinal (GI) carcinomas have a good prognosis if treated with surgery, diagnosis is often confirmed at a late stage and efficacious drugs are lacking. Recent progress in immune-based therapies has focused on dendritic cells (DCs), aiming to elicit tumor-specific responses by inducing immunological memory. Our previous microarray study indicated that a biomarker, termed lymphocyte antigen-6E (LY6E), is commonly overexpressed in two potentially lethal GI cancers: those of colon and stomach. In this study, we examined the antigenic potency of LY6E in stimulating DCs. Methods: Following isolation, differentiation, and maturation of mononuclear cells, DCs were pulsed with LY6E peptide, a protein related to major histocompatibility complex (MHC) class I/II. Subsequently, DCs were co-cultured with mouse splenocytes to assess antigen-specific T-cell proliferation. Elucidated cytotoxic T-lymphocyte responses were assessed using subcutaneous colorectal murine tumor models. Results: Our in vitro results suggest that DCs loaded with LY6E peptide antigen are capable of stimulating and inducing proliferation of murine T-cells. Furthermore, our in vivo results demonstrate that LY6E peptide has a substantial impact on provoking immune responses against induced colon cancer in mice. Discussion: In conclusion, based on the overexpression of LY6E in colorectal, gastric, and pancreatic cancers, the role of this peptide should be further investigated with a goal of developing new therapies for these challenging diseases.
    • Uncomfortably numb: suicide and the psychological undercurrent of COVID-19.

      Hughes, H; Macken, M; Butler, J; Synnott, K (2020-05-21)
    • Mindfulness moments for clinicians in the midst of a pandemic.

      Hedderman, E; O'Doherty, V; O'Connor, S (2020-05-21)
      Clinicians are routinely subjected to intense and stressful working environments, and the current COVID-19 crisis increases their risk of psychological distress. Mindfulness has been shown to improve life satisfaction, resilience to stress, self-compassion, compassion and general well-being in healthcare workers. Based on their clinical experience, the authors present mindfulness moments for clinicians (MMFC), a selection of short, simple and accessible mindfulness practices to promote resilience and compassion among clinicians working in this pandemic. The practices can be used on the job and are accessible to both novice and experienced meditators. Most of these practices are extracted from evidence-based mindfulness programmes. Further research is indicated to assess the effectiveness of using MMFC to support clinicians in their work and to promote resilience.