• 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.
    • 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.
    • Resuscitation for Cardiac Arrest and Postcardiac Arrest Care.

      Lin, Yan-Ren; Exadaktylos, Aristomenis K; Ng, Kee-Chong; Ryan, John M (2020-05-27)
    • Conservative management of complete traumatic pancreatic body transection; A case report.

      Duggan, W; Hannan, E; Brosnan, C; O'Sullivan, S; Conlon, K (2020-05-21)
      Introduction: Isolated pancreatic body transection secondary to blunt abdominal trauma is a very rare injury associated with poor outcomes. Almost all previously reported cases were managed by emergency distal pancreatectomy, which is associated with high morbidity and mortality. To our knowledge, this is the first reported case of complete transection of the pancreas at the body that was successfully treated by conservative management in an adult patient. Presentation of case: A 19-year-old male was found to have complete transection of the pancreatic body on computed tomography (CT) following blunt force abdominal trauma. Given that he was haemodynamically stable without evidence of haemorrhage or bile leakage on imaging, a trial of conservative management was initiated. He remained well through his admission, gradually improving clinically and biochemically with stable appearances on serial imaging. He remains asymptomatic as of six months since discharge from the hospital and continues to be monitored in the outpatient setting. Discussion: Management of pancreatic trauma with ductal injury has typically been with emergency distal pancreatectomy, which is associated with high morbidity and mortality. The decision to operate should not be purely based on radiological findings, and should take into account clinical status, haemodynamic stability, coexisting injuries and evidence of active haemorrhage or bile leak. Conclusion: In select cases, it is reasonable to trial conservative management in isolated traumatic pancreatic body fracture by means of close clinical observation and serial imaging. This may allow the patient to avoid a high-risk emergency distal pancreatectomy.
    • 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. (2020-05-14)
      Background: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. Methods: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. Results: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type. Conclusions: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women.
    • Poor prognostic factors in predicting abatacept response in a phase III randomized controlled trial in psoriatic arthritis.

      Mease, Philip J; McInnes, Iain B; Strand, Vibeke; FitzGerald, Oliver; Ahmad, Harris A; Elbez, Yedid; Banerjee, Subhashis (2020-04-30)
      In ASTRAEA (NCT01860976), abatacept significantly increased American College of Rheumatology criteria 20% (ACR20) responses at Week 24 versus placebo in patients with psoriatic arthritis (PsA). This post hoc analysis explored relationships between prospectively identified baseline characteristics [poor prognostic factors (PPFs) ] and response to abatacept. Patients were randomized (1:1) to receive subcutaneous abatacept 125 mg weekly or placebo for 24 weeks; those without ≥ 20% improvement in joint counts at Week 16 switched to open-label abatacept. Potential predictors of ACR20 response were identified by treatment arm using multivariate analyses. Likelihood of ACR20 response to abatacept versus placebo was compared in univariate and multivariate analyses in subgroups stratified by the PPF, as defined by EULAR and/or GRAPPA treatment guidelines. Odds ratios (ORs) were generated using logistic regression to identify meaningful differences (OR cut-off: 1.2). 424 patients were randomized and treated (abatacept n = 213; placebo n = 211). In abatacept-treated patients, elevated C-reactive protein (CRP), high Disease Activity Score based on 28 joints (CRP), presence of dactylitis, and ≥ 3 joint erosions were identified as predictors of response (OR > 1.2). In placebo-treated patients, only dactylitis was a potential predictor of response. In the univariate analysis stratified by PPF, ACR20 response was more likely (OR > 1.2) with abatacept versus placebo in patients with baseline PPFs than in those without; multivariate analysis confirmed this finding. Response to abatacept versus placebo is more likely in patients with features indicative of high disease activity and progressive disease; these characteristics are recognized as PPFs in treatment guidelines for PsA.
    • The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design.

      Angus, Derek C; Berry, Scott; Lewis, Roger J; Al-Beidh, Farah; Arabi, Yaseen; van Bentum-Puijk, Wilma; Bhimani, Zahra; Bonten, Marc; Broglio, Kristine; Brunkhorst, Frank; et al. (2020-04)
      There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform." The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.Clinical trial registered with www.clinicaltrials.gov (NCT02735707).
    • Smoking Prevalence and Secondhand Smoke Exposure during Pregnancy and Postpartum-Establishing Risks to Health and Human Rights before Developing a Tailored Programme for Smoking Cessation.

      Frazer, Kate; Fitzpatrick, Patricia; Brosnan, Mary; Dromey, Anne Marie; Kelly, Sarah; Murphy, Michael; O'Brien, Denise; Kelleher, Cecily C; McAuliffe, Fionnuala M (2020-03-12)
      Both smoking during pregnancy and secondhand smoke exposure are associated with reduced health outcomes. However, limited consistent evidence exists of risks of secondhand smoke exposure in pregnancy. Currently, inadequate smoking cessation services exist in Irish maternity hospitals. To identify the number of pregnant women smoking during pregnancy and to identify their exposure to secondhand smoke, we conducted a cross-sectional observational pilot study in one regional maternity hospital in Ireland in July/August 2018. Respondents were (1) women attending antenatal clinics and (2) postpartum women before discharge. Variables measured included smoking status of pregnant women and partner status, demographic variables, secondhand smoke exposure, and support for hospital smoke-free policy and development of smoking cessation services. The overall response rate was 42.2% in this study. The response rate was 56.5% (111/196) from postnatal wards and 37.3% (215/577) from antenatal clinics. Over 40% of respondents reported they had smoked during their lifetime. The majority of women (70%) reported quitting smoking before their pregnancy. Few women were active smokers. Almost 40% reported exposure to tobacco smoke in the previous week (38.5%); 16.9% reported living with a smoker, a critical factor in increased risk (Odds Ratio (OR) 3.89, 95% CI = 1.86-8.15, p < 0.001). Approximately 10% of postnatal mothers reported that their newborn would travel home with a smoker. Support for a no-smoking hospital policy was very high as was support for the development of cessation services. No documentation of secondhand smoke exposure for pregnant women or newborns is sought or recorded routinely in the hospital. A systems approach to develop smoking cessation programmes in maternity care should include screening and documenting of secondhand smoke exposure risks for women during pregnancy, and for their newborns at discharge, to improve health outcomes and protect human rights.
    • TIRADS Management Guidelines in the Investigation of Thyroid Nodules; Illustrating the Concerns, Costs, and Performance.

      Cawood, Tom James; Mackay, Georgia Rose; Hunt, Penny Jane; O'Shea, Donal; Skehan, Stephen; Ma, Yi (2020-03-10)
      Context: Ultrasound (US) risk-stratification systems for investigation of thyroid nodules may not be as useful as anticipated. Objective: We aimed to assess the performance and costs of the American College of Radiology Thyroid Image Reporting And Data System (ACR-TIRADS). Design settings and participants: We examined the data set upon which ACR-TIRADS was developed, and applied TR1 or TR2 as a rule-out test, TR5 as a rule-in test, or applied ACR-TIRADS across all nodule categories. We assessed a hypothetical clinical comparator where 1 in 10 nodules are randomly selected for fine needle aspiration (FNA), assuming a pretest probability of clinically important thyroid cancer of 5%. Results: The gender bias (92% female) and cancer prevalence (10%) of the data set suggests it may not accurately reflect the intended test population. Applying ACR-TIRADS across all nodule categories did not perform well, with sensitivity and specificity between 60% and 80% and overall accuracy worse than random selection (65% vs 85%). Test performance in the TR3 and TR4 categories had an accuracy of less than 60%. Using TR5 as a rule-in test was similar to random selection (specificity 89% vs 90%). Using TR1 and TR2 as a rule-out test had excellent sensitivity (97%), but for every additional person that ACR-TIRADS correctly reassures, this requires >100 ultrasound scans, resulting in 6 unnecessary operations and significant financial cost. Conclusions: Perhaps surprisingly, the performance ACR-TIRADS may often be no better than random selection. The management guidelines may be difficult to justify from a cost/benefit perspective. A prospective validation study that determines the true performance of TIRADS in the real-world is needed.
    • Neisseria meningitidis as a Cause of Septic Arthritis: An Unusual Case of Periprosthetic Joint Infection.

      Mc Carthy, A; Broderick, J M; Molloy, A P (2020-03-10)
      One of the most feared complications after arthroplasty is infection due to its significant impact on patient morbidity. Infection may transfer to the joint at the time of surgery or be seeded, haematologically, to the prosthetic joint from another infection source. In this case, a 72-year-old female presented with symptoms of septic arthritis seven years after her original arthroplasty surgery. At presentation, she denied trauma and any comorbidity which would predispose her to infection. Culturing of samples taken revealed the patient was infected with Neisseria meningitidis, and the patient underwent a DAIR procedure. She continued postoperative long-term antimicrobial therapy with resolution of her infection. Follow-up at one year showed complete resolution of the patient's illness with a return to premorbid baseline. To our knowledge, this is the third reported case of septic arthritis caused by Neisseria meningitidis in a prosthetic joint in the literature.
    • Real-world experience of leadless left ventricular endocardial cardiac resynchronization therapy: A multicenter international registry of the WiSE-CRT pacing system.

      Sieniewicz, Benjamin J; Betts, Timothy R; James, Simon; Turley, Andrew; Butter, Christian; Seifert, Martin; Boersma, Lucas V A; Riahi, Sam; Neuzil, Petr; Biffi, Mauro; et al. (2020-03-09)
      Background: Biventricular endocardial pacing (BiV ENDO) is a therapy for heart failure patients who cannot receive transvenous epicardial cardiac resynchronization therapy (CRT) or have not responded adequately to CRT. BiV ENDO CRT can be delivered by a new wireless LV ENDO pacing system (WiSE-CRT system; EBR Systems, Sunnyvale, CA), without the requirement for lifelong anticoagulation. Objective: The purpose of this study was to assess the safety and efficacy of the WiSE-CRT system during real-world clinical use in an international registry. Methods: Data were prospectively collected from 14 centers implanting the WiSE-CRT system as part of the WiCS-LV Post Market Surveillance Registry. (ClinicalTrials.gov Identifier: NCT02610673). Results: Ninety patients from 14 European centers underwent implantation with the WiSE-CRT system. Patients were predominantly male, age 68.2 ± 10.5 years, left ventricular ejection fraction 30.6% ± 8.9%, mean QRS duration 180.7 ± 27.0 ms, and 40% with ischemic etiology. Successful implantation and delivery of BiV ENDO pacing was achieved in 94.4% of patients. Acute (<24 hours), 1- to 30-day, and 1- to 6-month complications rates were 4.4%, 18.8%, and 6.7%, respectively. Five deaths (5.6%) occurred within 6 months (3 procedure related). Seventy percent of patients had improvement in heart failure symptoms. Conclusion: BiV ENDO pacing with the WiSE-CRT system seems to be technically feasible, with a high success rate. Three procedural deaths occurred during the study. Procedural complications mandate adequate operator training and implantation at centers with immediately available cardiothoracic and vascular surgical support.
    • ERS International Congress, Madrid, 2019: highlights from the Basic and Translational Science Assembly.

      Ubags, Niki D; Baker, Jonathan; Boots, Agnes; Costa, Rita; El-Merhie, Natalia; Fabre, Aurélie; Faiz, Alen; Heijink, Irene H; Hiemstra, Pieter S; Lehmann, Mareike; et al. (2020-03-02)
      In this review, the Basic and Translational Sciences Assembly of the European Respiratory Society (ERS) provides an overview of the 2019 ERS International Congress highlights. In particular, we discuss how the novel and very promising technology of single cell sequencing has led to the development of a comprehensive map of the human lung, the lung cell atlas, including the discovery of novel cell types and new insights into cellular trajectories in lung health and disease. Further, we summarise recent insights in the field of respiratory infections, which can aid in a better understanding of the molecular mechanisms underlying these infections in order to develop novel vaccines and improved treatment options. Novel concepts delineating the early origins of lung disease are focused on the effects of pre- and post-natal exposures on neonatal lung development and long-term lung health. Moreover, we discuss how these early life exposures can affect the lung microbiome and respiratory infections. In addition, the importance of metabolomics and mitochondrial function analysis to subphenotype chronic lung disease patients according to their metabolic program is described. Finally, basic and translational respiratory science is rapidly moving forward and this will be beneficial for an advanced molecular understanding of the mechanisms underlying a variety of lung diseases. In the long-term this will aid in the development of novel therapeutic targeting strategies in the field of respiratory medicine.
    • Effectiveness and cost of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in obesity services (STRIVE study): study protocol of an open-label, real-world, randomised, controlled trial.

      Papamargaritis, Dimitris; Al-Najim, Werd; Lim, Jonathan; Crane, James; Lean, Mike; le Roux, Carel; McGowan, Barbara; O'Shea, Donal; Webb, David; Wilding, John; et al. (2020-02-13)
      In this 2-year, multicentre, open-label, real-world randomised controlled trial, 384 adults with severe and complex obesity (defined as body mass index ≥35 kg/m2 plus either prediabetes, type 2 diabetes, hypertension or sleep apnoea) will be randomised via a 2:1 ratio to receive either standard SWMS care (n=128) or standard SWMS care plus a targeted prescribing pathway for LIRA 3 mg with prespecified stopping rules at 16, 32 and 52 weeks (n=256).The primary outcome is to compare the proportion of participants achieving a weight loss of ≥15% at 52 weeks with a targeted prescribing pathway versus standard care. Secondary outcomes include a comparison of (1) the weight loss maintenance at 104 weeks and (2) the budget impact and cost effectiveness between the two groups in a real-world setting.
    • An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis across Phase III and Long-Term Extension Studies with Comparison to Real-World Observational Data.

      Burmester, Gerd R; Curtis, Jeffrey R; Yun, Huifeng; FitzGerald, Oliver; Winthrop, Kevin L; Azevedo, Valderilio F; Rigby, William F C; Kanik, Keith S; Wang, Cunshan; Biswas, Pinaki; et al. (2020-01-31)
      Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). Objective: Our objective was to compare the incidence rates (IRs) of adverse events in tofacitinib clinical trials and real-world observational data for alternative treatments. Methods: The tofacitinib "dose-comparison cohort" included months 0-12 of two phase III studies (tofacitinib 5 [n = 238] and 10 [n = 236] mg twice daily [BID]); the "all-tofacitinib comparison cohort" (n = 783) included two phase III and one ongoing long-term extension study (data cutoff May 2016). An "observational comparison cohort" (n = 5799) comprised patients initiating a conventional synthetic disease-modifying antirheumatic drug (DMARD), biologic DMARD, or apremilast in the US Truven MarketScan database from 2010 to 2015. IRs for serious infections (SIEs; requiring hospitalization), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, and major adverse cardiovascular events (MACE) across cohorts were qualitatively compared. Results: IRs (patients with events/100 patient-years) for SIEs were similar between the tofacitinib dose-comparison cohort (5 mg BID: 1.3; 10 mg BID: 2.0) and the observational comparison cohort (1.1-7.9; treatment dependent). The tofacitinib dose-comparison cohort had a higher rate of HZ (5 mg BID: 2.0; 10 mg BID: 2.7) than did the observational comparison cohort (0.8-2.0). IRs for NMSC were generally lower in the all-tofacitinib comparison cohort (0.5) than in the observational comparison cohort (0.4-6.0). IRs for MACE, malignancies excluding NMSC, and NMSC were similar between cohorts. Conclusion: In patients with PsA, tofacitinib had a safety profile similar to that of other systemic therapies in real-world settings, except for the risk of HZ, a known risk of tofacitinib.
    • Sacubitril-Valsartan in a routine community population: attention to volume status critical to achieving target dose.

      Pharithi, Rebabonye B; Ferre-Vallverdu, Maria; Maisel, Alan S; O'Connell, Eoin; Walshe, Myra; Sweeney, Claire; Barton, James; McDonald, Kathrine; O'Hare, Daniel; Watson, Chris; et al. (2020-01-05)
      This is a retrospective single-centre review of patients switched from angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to sacubitril-valsartan between May 2016 and August 2018. Baseline and follow-up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril-valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril-valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril-valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD.
    • A Temporal Comparative Study of Women’s Rugby Injuries Presenting to an Emergency Department

      Gilmartin, S.; Ryan, J. (Irish Medical Journal, 2019-10)
      We aimed to examine the change in injury patterns, diagnostics and treatments provided to female rugby players in an emergency department between two separate seasons ten years apart.
    • The Role of Interventional Radiology in the Management of Obstetric and Gynaecological Haemorrhage

      O’Brien, C.; Healy, G.M.; Anglim, B.C.; O’Brien, A.; Duignan, J.; Patel, A.; Cheung, M.; Cantwell, C.P. (Irish Medical Journal, 2019-07)
      Aim We will review our experience of emergent arterial embolization used to treat haemodynamically unstable patients with obstetric and gynaecological haemorrhage. Methods This is a retrospective study of patients with haemodynamically unstable obstetric and gynaecological haemorrhage treated with emergent arterial embolization from 2010 to 2015. Results 22 patients (average age 41 (SD +/-9) years) had emergent arterial embolization. 63% had post-partum haemorrhage(PPH). 82% of cases were performed with conscious sedation and local anaesthesia. Embolization was technically successful in all cases. Embolization was clinically successful in 95% (21/22). In one case of PPH the patient represented six days later with recurrent bleeding and was treated with surgical suturing of the cervix. There were no complications or deaths. Conclusion Arterial embolization is a highly successful treatment of obstetric and gynaecological haemorrhage in unstable patients.