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Background:\ud The PARAMEDIC cluster randomised trial evaluated the LUCAS mechanical chest compression device, and did not find evidence that use of mechanical chest compression led to an improvement in survival at 30 days. This paper reports patient outcomes from admission to hospital to 12 months after randomisation.\ud \ud Methods:\ud Information about hospital length of stay and intensive care management was obtained through linkage with Hospital Episode Statistics and the Intensive Care National Audit and Research Centre. Patients surviving to hospital discharge were approached to complete questionnaires (SF-12v2, EQ-5D, MMSE, HADS and PTSD-CL) at 90 days and 12 months. The study is registered with Current Controlled Trials, number ISRCTN08233942.\ud \ud Results:\ud 377 patients in the LUCAS arm and 658 patients in the manual chest compression were admitted to hospital. Hospital and intensive care length of stay were similar. Long term follow-up assessments were limited by poor response rates (53.7% at 3 months and 55.6% at 12 months). Follow-up rates were lower in those with worse neurological function. Among respondents, long term health related quality of life outcomes and emotional well-being was similar between groups. Cognitive function, measured by MMSE, was marginally lower in the LUCAS arm mean 26.9 (SD 3.7) compared to control mean 28.0 (SD 2.3), adjusted mean difference −1.5 (95% CI −2.6 to −0.4).\ud \ud Conclusion:\ud There were no clinically important differences identified in outcomes at long term follow-up between those allocated to the mechanical chest compression compared to those receiving manual chest compression.

The diffusion and democratisation of computing technologies and physical prototyping systems has supported the rise of Do-It-Yourself culture. In the context of design innovation, this shift has undoubtedly blurred the lines between the roles of amateur and professional. Crowdsourcing platforms providing easily accessible, lightweight services to promote and fund ideas for new products can potentially radically compress the timescale from new concept generation to market. However, questions are emerging around these adjustments in the roles of amateur and professional, and to what extend individual makers and their communities can participate in, and benefit from, this new landscape. This paper will examine this situation using the framing of a “toolkit design and development” approach. We discuss the toolkit approach by drawing on the work of a current cross-European, interdisciplinary, collaborative project that is developing a technology toolkit to enable creation of locally based DIY networkin...

This paper outlines a thesis that seeks to understand how people's experiences of places in the urban environment that are meaningful to them on a personal level, and in particular their stories and emotions connected to those personally significant places, could potentially inform the design of future technological devices and services. This urban HCI study aims to investigate the different forms this data could take, and the potential for sharing and exploring this personal data with other people using emotion maps. In this paper we introduce the methodology designed to this end, and report on some of the findings of our initial pilot study.

Background Inflammatory bowel disease (IBD) is refractory to treatment in one-half of patients. Aims To evaluate the occurrence of suboptimal therapy among patients with IBD treated with tumor necrosis factor antagonists (anti-TNFs). Methods A multinational chart review in Europe and Canada was conducted among IBD patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) who initiated anti-TNF therapy between 2009 and 2013. The primary endpoint was the cumulative incidence of suboptimal therapy during a two-year follow-up period, defined by the presence of the following indicators: dose escalation, discontinuation, switching, non-biologic therapy escalation, or surgery. Results The study included 1195 anti-TNF initiators (538 UC and 657 CD). The majority of patients (64% of UC and 58% of CD) had at least one indicator of suboptimal therapy. The median time to suboptimal therapy indicator was 12.5 and 17.5 months for UC and CD patients, respectively. Among the 111 UC and 174 CD anti-TNF switchers, 51% and 56% had an indicator of suboptimal therapy, respectively. The median time to suboptimal therapy indicator with the second anti-TNF was 14.3 and 13.0 months for UC and CD patients, respectively. Conclusion The majority of IBD patients showed suboptimal therapy with current anti-TNFs.

BackgroundMechanical chest compression devices may help to maintain high-quality cardiopulmonary resuscitation (CPR), but little evidence exists for their effectiveness. We evaluated whether or not the introduction of Lund University Cardiopulmonary Assistance System-2 (LUCAS-2; Jolife AB, Lund, Sweden) mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest (OHCA).ObjectiveEvaluation of the LUCAS-2 device as a routine ambulance service treatment for OHCA.DesignPragmatic, cluster randomised trial including adults with non-traumatic OHCA. Ambulance dispatch staff and those collecting the primary outcome were blind to treatment allocation. Blinding of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. We also conducted a health economic evaluation and a systematic review of all trials of out-of-hospital mechanical chest compression.SettingFour UK ambulance services (West Midlands, North East England, Wales and South Central), comprising 91 urban and semiurban ambulance stations. Clusters were ambulance service vehicles, which were randomly assigned (approximately 1 : 2) to the LUCAS-2 device or manual CPR.ParticipantsPatients were included if they were in cardiac arrest in the out-of-hospital environment. Exclusions were patients with cardiac arrest as a result of trauma, with known or clinically apparent pregnancy, or aged InterventionsPatients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene.Main outcome measuresSurvival at 30 days following cardiac arrest; survival without significant neurological impairment [Cerebral Performance Category (CPC) score of 1 or 2].ResultsWe enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 device and 2819 assigned to control) between 15 April 2010 and 10 June 2013. A total of 985 (60%) patients in the LUCAS-2 group received mechanical chest compression and 11 (LimitationsThere was substantial non-compliance in the LUCAS-2 arm. For 272 out of 1652 patients (16.5%), mechanical chest compression was not used for reasons that would not occur in clinical practice. We addressed this issue by using complier average causal effect analyses. We attempted to measure CPR quality during the resuscitation attempts of trial participants, but were unable to do so.ConclusionsThere was no evidence of improvement in 30-day survival with LUCAS-2 compared with manual compressions. Our systematic review of recent randomised trials did not suggest that survival or survival without significant disability may be improved by the use of mechanical chest compression.Future workThe use of mechanical chest compression for in-hospital cardiac arrest, and in specific circumstances (e.g. transport), has not yet been evaluated.TriaI registrationCurrent Controlled Trials ISRCTN08233942.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 11. See the NIHR Journals Library website for further project information.

Background and Aims: The GEMINI long-term safety (LTS) study is a continuing phase 3 trial investigating the safety and efficacy of vedolizumab, an α4β7 integrin antagonist for ulcerative colitis (UC) and Crohn’s disease. We provide an interim analysis of efficacy in patients with UC. Methods: Patients from the C13004 and GEMINI 1 studies and a cohort of vedolizumab-naive patients received open-label vedolizumab every 4 weeks. Interim data were collected from 22 May 2009 to 27 June 2013. Clinical response and remission, evaluated using partial Mayo scores, and health-related quality of life (HRQL) were assessed for up to 152 weeks of cumulative treatment in the efficacy population. Results: As of 27 June 2013, 63% of the efficacy population (n=532/845) were continuing treatment. Among patients who responded to vedolizumab induction and had data available, 88% (n=120/136) were in remission after 104 weeks of exposure (96% [n=70/73] after 152 weeks). Among patients who withdrew from every-8-week vedolizumab maintenance in GEMINI 1 (n=32) before week 52, increased dosing to every 4 weeks in GEMINI LTS resulted in response and remission rates of 41% and 28%, respectively, after 52 weeks, an increase from 19% and 6%, respectively, from before the dose increase. Similar benefits were demonstrated regardless of prior tumour necrosis factor-antagonist exposure. Durable benefits on HRQL were also observed. Conclusions: Patients with UC experienced clinical and HRQL improvements with continued vedolizumab treatment. Increased dosing frequency to every 4 weeks was beneficial in patients who had loss of response to 8-weekly dosing. ClinicalTrials.gov ID [NCT00790933][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00790933&atom=%2Feccojc%2Fearly%2F2016%2F09%2F28%2Fecco-jcc.jjw177.atom

Background and Aims: Vedolizumab is a gut-selective α4β7 integrin antagonist therapy for ulcerative colitis and Crohn’s disease. The GEMINI long-term safety (LTS) trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohn’s disease. Methods: Patients from the C13004, GEMINI 2, and GEMINI 3 studies and vedolizumab-naive patients could enrol in GEMINI LTS and received vedolizumab every 4 weeks. Data were collected from 22 May 2009 to 27 June 2013. Outcomes of clinical response and remission, defined by the Harvey-Bradshaw Index, and health-related quality of life (HRQL) were assessed for up to 152 weeks of treatment in the efficacy population. Results: Among patients with response at week 6 in GEMINI 2 who received vedolizumab continuously, 83% (n=100/120) and 89% (n=62/70) of patients with available data were in remission after 104 and 152 weeks, respectively. Increased dosing frequency from every 8 weeks (GEMINI 2) to every 4 weeks (GEMINI LTS) improved outcomes in patients who had withdrawn early from GEMINI 2, with 47% (n=27/57) experiencing clinical response and 32% (n=18/57) in remission at week 52 of GEMINI LTS (up from 39% and 4% before the dose increase). Similar improvements were observed regardless of prior tumour necrosis factor (TNF)-antagonist exposure. Long-term benefits of HRQL were also observed. Conclusions: The clinical benefits of vedolizumab continued with long-term treatment regardless of prior TNF antagonist exposure. Increased dosing frequency might improve outcomes in patients who lose response to conventional 8-weekly dosing. ClinicalTrials.gov ID [NCT00790933][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00790933&atom=%2Feccojc%2Fearly%2F2016%2F09%2F28%2Fecco-jcc.jjw176.atom

This article was migrated. The article was marked as recommended. The choice of a future career specialty has always been a stressful decision for medical students. To mitigate this stress and assist students in making more informed career decisions we developed the Pre-clerkship Residency Exploration Program (PREP), a two-week summer elective program that provides students with the opportunity to gain exposure to specialities that traditionally do not receive a lot of attention in medical school. To initiate this student led program we faced many obstacles, suffered many failures, learned a tremendous amount and eventually found success. In this article, we offer 12 tips on how to create a medical education program that is sustainable, effective and receives strong buy-in from faculty and administration. Our tips come from the perspective of students starting their own program but are translatable to anyone interested in taking an innovative idea and seeing it through to fruition.

BackgroundSepsis is a common condition which kills approximately 44,000 people annually in the UK. Early recognition and management of sepsis has been shown to reduce mortality and improve outcomes. Paramedics frequently attend patients with sepsis, and are well placed to provide early diagnosis and treatment. We aimed to assess whether a multi-centre randomised trial to evaluate pre-hospital antibiotics was feasible.MethodsVolunteer paramedics used scratchcards to allocate patients with ‘Red Flag’ Sepsis at random between experimental and control arms. The primary outcome was mortality at six months. We also measured: adverse events, costs, final diagnosis, length of stay in hospital, and quality of care; and collected qualitative data about acceptability to patients in interviews, and paramedics in focus groups. We pre-specified criteria for deciding whether to progress to a fully powered trial based on: recruitment of paramedics and patients; retrieval of outcome data; safety; acceptability; and diagnostic accuracy.ResultsFifty-four paramedics completed their training and were issued scratchcards to randomly allocate patients to trial arms. Patients were recruited from 1.12.17 to 31.5.18. In total, 118 patients were randomly allocated to trial arms; four patients dissented to be included in the trial, leaving 114 patients to follow-up. Sixty-two patients (54%) were allocated to the intervention arm. The mean age of the control arm was 71.2 years (range 28–97); 33 (65%) control participants were female. In the intervention arm the mean age was 75.6 years (range 30–99) and 38 patients (61%) were female. Nine patients in the control group (18%) and 17 in the intervention group (28%) were already taking antibiotics at the time of their 999 call. Twenty-three questionnaires were received. No serious adverse events were reported.ConclusionsComplete results will be presented at the time of the conference, when routine linked anonymised outcomes are available.

This article explores approaches to envisionment in the field of interaction design. Design fictions are introduced as a method to articulate future possibilities. Three case studies are described which explore interaction in public space. The fictions create imaginative projections with the intention of generating reaction and responses in the public that will lead to a greater understanding of the physical and conceptual design space. The first case study explored how citizens could anonymously comment on their relationship with a city. The second study encouraged participants to reflect on their habits and rituals and to view these through fresh eyes. The final case study sought to surprise and engage gallery visitors through an interactive piece that raised issues concerning the surreptitious capture of data. The paper concludes by reflecting on the utility of design fictions and the role they can play in concept envisionment.

Background Biological therapies are increasingly used to treat ulcerative colitis (UC). Aim To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. Methods A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Results Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naive patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35–3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49–5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21–4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients ‘straight through’. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14–9.20], golimumab 2.33 [1.04–5.41], and adalimumab 3.96 [1.67–9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36–41.0]). Conclusions This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest.This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant.8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes).Trial registration (ISRCTN73485024).

Objective: Early identification of sepsis could enable prompt delivery of key interventions such as fluid resuscitation and antibiotic administration which, in turn, may lead to improved patient outcomes. Limited data indicate that recognition of sepsis by paramedics is often poor. We systematically reviewed the literature on prehospital sepsis screening tools to determine whether they improved sepsis recognition.\ud \ud Design: Systematic review. The electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed were systematically searched up to June 2015. In addition, subject experts were contacted.\ud \ud Setting: Prehospital/emergency medical services (EMS).\ud \ud Study selection: All studies addressing identification of sepsis (including severe sepsis and septic shock) among adult patients managed by EMS.\ud \ud Outcome measures: Recognition of sepsis by EMS clinicians.\ud \ud Results: Owing to considerable variation in the methodological approach adopted and outcome measures reported, a narrative approach to data synthesis was adopted. Three studies addressed development of prehospital sepsis screening tools. Six studies addressed paramedic diagnosis of sepsis with or without use of a prehospital sepsis screening tool.\ud \ud Conclusions: Recognition of sepsis by ambulance clinicians is poor. The use of screening tools, based on the Surviving Sepsis Campaign diagnostic criteria, improves prehospital sepsis recognition. Screening tools derived from EMS data have been developed, but they have not yet been validated in clinical practice. There is a need to undertake validation studies to determine whether prehospital sepsis screening tools confer any clinical benefit.

BACKGROUND: Mechanical chest compression devices have the potential to help maintain high-quality cardiopulmonary resuscitation (CPR), but despite their increasing use, little evidence exists for their effectiveness. We aimed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest. METHODS: The pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARAMEDIC) trial was a pragmatic, cluster-randomised open-label trial including adults with non-traumatic, out-of-hospital cardiac arrest from four UK Ambulance Services (West Midlands, North East England, Wales, South Central). 91 urban and semi-urban ambulance stations were selected for participation. Clusters were ambulance service vehicles, which were randomly assigned (1:2) to LUCAS-2 or manual CPR. Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat. Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation. Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. The study is registered with Current Controlled Trials, number ISRCTN08233942. FINDINGS: We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 group, 2819 assigned to the control group) between April 15, 2010 and June 10, 2013. 985 (60%) patients in the LUCAS-2 group received mechanical chest compression, and 11 (

Aim This study explores why resuscitation is withheld when emergency medical staff arrive at the scene of a cardiac arrest and identifies modifiable factors associated with this decision. Methods This is a secondary analysis of unselected patients who sustained an out of hospital cardiac arrest attended by ambulance vehicles participating in a randomized controlled trial of a mechanical chest compression device (PARAMEDIC trial). Patients were categorized as ‘non-resuscitation’ patients if there was a do-not-attempt-cardiopulmonary-resuscitation (DNACPR) order, signs unequivocally associated with death or resuscitation was deemed futile (15 min had elapsed since collapse with no bystander-CPR and asystole recorded on EMS arrival). Results Emergency Medical Services attended 11,451 cardiac arrests. Resuscitation was attempted or continued by Emergency Medical Service staff in 4805 (42%) of cases. Resuscitation was withheld in 6646 cases (58%). 711 (6.2%) had a do not attempt resuscitation decision, 4439 (38.8%) had signs unequivocally associated with death and in 1496 cases (13.1%) CPR was considered futile. Those where resuscitation was withheld due to futility were characterised by low bystander CPR rates (7.2%) and by being female. Conclusions Resuscitation was withheld by ambulance staff in over one in ten (13.1%) victims of out of hospital cardiac arrest on the basis of futility. These cases were associated with a very low rate of bystander CPR. Future studies should explore strengthening the ‘Chain of Survival’ to increase the community bystander CPR response and evaluate the effect on the numbers of survivors from out of hospital cardiac arrest.

The effectiveness of phosphate binders can be assessed by evaluating urinary phosphorus excretion in healthy volunteers, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. Healthy volunteers were enrolled into one of five separate randomized trials; four were open label and one double blind. Following a screening period of ≤28 days, participants received differing tablets containing lanthanum carbonate [LC, 3000 mg/day of elemental lanthanum (in one study other doses were also used)]. Participants received a standardized phosphate diet and remained in the relevant study center throughout the duration of each treatment period. The end point in all studies was the reduction in urinary phosphorus excretion. Reductions in mean 24-h urinary phosphorus excretion in volunteers receiving a lanthanum dose of 3000 mg/day were between 236 and 468 mg/day over the five separate studies. These data in healthy volunteers can be used to estimate the amount of reduction of dietary phosphate absorption by LC. The reduction in 24-h urinary phosphorus excretion per tablet was compared with published data on other phosphate binders. Although there are limitations, evidence suggests that LC is a very effective phosphate binder in terms of binding per tablet.

Objective To assess the cost-effectiveness of lanthanum carbonate (LC) versus sevelamer hydrochloride (SH) as a treatment for hyperphosphatemia in end-stage renal disease (ESRD) patients. Methods A Markov model was developed to estimate health outcomes; quality-adjusted life years (QALYs) and life-years saved (LYS), as well as associated costs. The model incorporated patient-level data from a randomized head-to-head crossover study that compared the reduction of serum phosphorus using LC and SH for 4 weeks each. The model included patients previously treated with calcium-based binders. Both the intent-to-treat (ITT) population and the cohort of patients who completed treatment in both periods of the study (i.e., completer population) were assessed. The baseline risks of cardiovascular disease (CVD), all-cause mortalities for CVD, and non-CVD patients were derived from a large US renal database. Patient outcomes were modeled for 10 years, and incremental cost-effectiveness ratios (ICERs) were calculated for LC relative to SH. Deterministic and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the base-case model. Results For the ITT population, the ICERs of LC versus SH were $24,724/QALY and $15,053/LYS, respectively (in US dollars). When the completer population was considered, the ICERs of LC versus SH were $15,285/QALY and $9,337/LYS (Table 2), respectively. The PSA indicated 61.9% and 85.8% probabilities for ITT and completer populations of LC being cost-effective at the $50,000/QALY willingness-to-pay threshold, respectively. Conclusion LC is a cost-effective strategy compared with SH in the treatment of ESRD patients with hyperphosphatemia who were previously treated with calcium-based binders. Sensitivity analyses demonstrated the robustness of the pharmacoeconomic model.

Die Basismasnahmen zur Wiederbelebung („basic life support“, BLS) beziehen sich auf das Freihalten der Atemwege sowie das Aufrechterhalten von Atmung und Kreislauf ohne Verwendung von Hilfsmitteln, abgesehen von einfachen Mitteln zum Eigenschutz [1]. Diese Sektion enthalt die Leitlinien zu den Basismasnahmen zur Wiederbelebung Erwachsener und zur Verwendung eines automatisierten externen Defibrillators (AED). Sie beinhaltet auch das Erkennen des plotzlichen Herztodes, die stabile Seitenlage und das Handeln bei Ersticken (Verlegung der Atemwege durch Fremdkorper). Leitlinien fur den Einsatz von manuellen Defibrillatoren und zur Einleitung von Wiederbelebungsmasnahmen im Krankenhaus finden sich in den Sektionen 3 und 4 [2, 3].

Background. Lanthanum carbonate and sevelamer carbonate are non-calcium-based phosphate binders used to manage hyperphosphataemia in patients with chronic kidney disease (CKD). Patients with CKD may require intravenous or oral active vitamin D. We investigated the effects of lanthanum carbonate and sevelamer carbonate on the bioavailability of oral calcitriol. Methods. This was a three-period, crossover study in healthy volunteers. Forty-one individuals were randomized to one of six possible sequences, each consisting of three treatment periods separated by washouts. The treatments were calcitriol (1 μg at lunch), calcitriol with lanthanum carbonate (3000 mg/day) and calcitriol with sevelamer carbonate (7200 mg/day). Serum calcitriol levels were assessed at baseline and throughout the study. Results. Co-administration of lanthanum carbonate with calcitriol had no significant effect on area under the curve over 48 h (AUC0–48) for serum exogenous calcitriol [least-squares (LS) mean, calcitriol with lanthanum carbonate vs calcitriol alone: 429 pg h/mL vs 318 pg h/mL, respectively; P = 0.171]. Similarly, there was no significant effect on maximum concentration (Cmax). In contrast, co-administration with sevelamer was associated with a significant reduction in bioavailability parameters for calcitriol (calcitriol with sevelamer carbonate vs calcitriol alone, LS mean AUC0–48: 137 pg h/mL vs 318 pg h/mL, respectively; P = 0.024; LS mean Cmax: 40.1 pg/mL vs 49.7 pg/mL, respectively; P < 0.001). Conclusions. Sevelamer carbonate significantly reduces serum concentrations of exogenous calcitriol when administered concomitantly with oral calcitriol, whereas lanthanum carbonate has no significant effect. This should be considered when treating CKD patients who require phosphate binders and oral vitamin D.

Epidemiological data link elevated levels of serum phosphorus with increased mortality among patients with chronic kidney disease. Recent data also suggest improved survival with the use of dietary phosphate binders in patients on dialysis. However, few studies have comprehensively evaluated the survival benefit associated with different phosphate binders. A post-hoc survival analysis was undertaken of lanthanum carbonate (Fosrenol *) versus standard therapy.Patients on dialysis enrolled in a phase 3, 2-year, comparative safety study were randomized 1:1 to lanthanum carbonate or standard therapy to treat serum phosphorus to a target ofor =5.9 mg/dL (1.90 mmol/L). Patients (N = 1354) were followed up for survival status during, or after completion of or discontinuation from the study.Survival was measured by time from first dose of study medication to all-cause mortality or last contact.The distribution of follow-up time was similar in the lanthanum carbonate and standard therapy groups (mean 23.7 versus 23.9 months [median 27.0 versus 26.0 months], respectively). Serum phosphorus levels were similar across treatment groups, as patients were treated to target. At follow-up, 19.9% (135/680) of patients treated with lanthanum carbonate had died versus 23.3% (157/674) on standard therapy (log-rank p = 0.18). In the subgroup of patients aged65 years (n = 336), 27.0% (44/163) of lanthanum-carbonate-treated patients had died compared with 39.3% (68/173) on standard therapy (log-rank p = 0.04).In these survival analyses, overall mortality was similar in the lanthanum carbonate and standard therapy groups, but results suggest that there was a survival benefit associated with lanthanum carbonate treatment for patients aged65 years, who are likely to carry the greatest burden of vascular calcification. These results were similar to those observed in the Dialysis Clinical Outcomes Revisited study, a prospective trial of sevelamer hydrochloride designed to assess survival.

(2009). The Public Law of Commercial Regulation. Judicial Review: Vol. 14, No. 2, pp. 197-209.

This paper argues for a consistent and new design-specific disciplinary framework that will provide a better understanding of emergent design practice. Design today is characterised by a blurring of traditional design domains (Sanders 2006) and design activities that are backed by other subject specialist areas such as computing, electronics or bioengineering. In order to understand and facilitate collaborative working, a consistent disciplinary framework is required. Furthermore, in understanding complex disciplinary influences this framework provides a method of delineating and analysing emergent practice. To derive the framework this paper explores the existing literature on disciplinary terms. Contemporary creative design practice is then analysed via this taxonomy. To this end, the paper argues that through consistent use of the terms, ‘multidisciplinary design’, ‘crossdisciplinary design’, ‘interdisciplinary design’ and ‘transdisciplinary design’, distinctions can be made within the increasingly com...

Sepsis is a systemic response to infection, which may progress to severe sepsis and septic shock (1). It is a global health problem that carries a huge economic burden (2, 3). The last decade has seen a significant drive to improve outcomes for patients with sepsis, with substantial effort focused on intensive care unit (ICU) and emergency department (ED) patients in particular. Recent data have indicated that ward patients who develop sepsis have worse outcomes than ICU or ED patients (4, 5), which has led to efforts to improve sepsis recognition in the ward environment to enable prompt intervention.

The City | Data | Future installation is a collection of "design fiction" video scenarios that speculate about the experience of urban life and how it might change in the near future. These visions were collaboratively created over the course of an interdisciplinary summer school, exploring the emergent field of urban interaction design. The focus of this field is public space and the relationships between people -- with and through technology. Cities in the future will contain a tangled mesh of interlocking data streams, and this complexity is increasingly forming the backdrop to human activities. The installation presents a series of works that invite the viewer to consider how technology might shape the city of the future and subsequently, our relationship with the city, and with each other. The works have been created as part of the UrbanIxD project, which ran between 2013-14 and was funded under the EU FP7 FET Open initiative.

This chapter describes an approach to the development of virtual representations of real places. The work was funded under the European Union’s €20m Future and Emerging Technologies theme of the 5th Framework Programme, “Presence”, 2002 - 2005. The aim of the project, called BENOGO, was to develop a novel technology based on real-time image-based rendering (IBR) for representing places in virtual environments. The specific focus of the work presented here concerned how to capture the essential features of real places, and how to represent that knowledge, so that the team developing the IBR-based virtual environments could produce an environment that was as realistic as possible. This involved the development and evaluation of a number of virtual environments and the evolution of two complementary techniques; the Place Probe and Patterns of place.

Urban Interaction Design draws upon knowledge and approaches from a range of disciplines involved in the design of urban spaces, connecting them and establishing their interactions as a principle. It is also rooted in the wider field of interaction design, from which it takes much of its emphasis on behaviors at the human scale, putting the citizen at the center of the process of creating solutions in networked urban spaces. The paper presents the results of a preliminary survey that seeks to articulate, through best case examples, the challenges and opportunities for the field of Urban Interaction Design in the context of Smart Cities.

This paper describes the design, application, and refinement of a qualitative tool designed to study sense of place. The Place Probe incorporates a range of stimuli and techniques aimed at articulating a person's sense of place. It has been developed, used, and undergone three revisions. The paper describes the background to the choice of measures that were included in the Place Probe and describes its application in both a physical place and a virtual representation of that place. This enables a comparison of the experiences. An analysis of the results reveals a similarity of reported experience, however the extremes experienced in the physical place were less pronounced in the virtual representation. The Place Probe has been refined in light of the results of the empirical work and now incorporates both qualitative and quantitative data on the experience of place.

This paper presents work undertaken as part of an ongoing research programme into wearable computers and the processes for designing personal digital artifacts that exhibit authenticity. Authenticity is discussed in its associations with contemporary craft and as a means by which tools may cease disappearing in the obsessively rational quest for the 'invisible computer' and instead become more meaningful for users as objects in interaction. Materiality is arrived at as a possible basis for further work into agentive design methodologies.

Introduction Ulcerative colitis (UC) patients treated with tumour necrosis factor antagonists (anti-TNFs) may require therapy changes over time, which may be considered as indicators of suboptimal therapy. Methods A multinational, multicentre, retrospective, chart review study was conducted to assess the indicators of suboptimal therapy among adult UC patients receiving their first anti-TNF [infliximab (IFX) or adalimumab (ADA)] between June 2009 and June 2013 (index therapy). The indicators of suboptimal therapy during 2 year follow up included: anti-TNF dose-escalation (assessed >4 months after index to allow for initial dose adjustments), augmentation with non-biologic therapy, UC-related surgery, discontinuation of first anti-TNF and switching to second anti-TNF. Dose escalation was defined as any increase in dose and/or frequency of the index anti-TNF agent(s). Augmentation was defined as starting a new non-biologic drug or increase in dose/frequency of the concurrent non-biological drugs with anti-TNF therapy. Discontinuation of index anti-TNF was based on entry in patients’ charts and excluded patients who discontinued anti-TNF despite it being effective during the follow-up period. Switch was defined as a subset of discontinuation patients who initiated another anti-TNF therapy over the follow-up period. The number and percentage of patients with each indicator and ≥1 indicator was summarised descriptively by country. Results The study included 538 UC patients with mean age (SD) of 42 (14) years. Forty-seven percent of patients were females and 73% reported moderate to severe UC at index. The percentages of patients on IFX and ADA as first anti-TNF were 92% and 8%, respectively. Overall, within 2 years, 61% of UC patients had ≥1 indicator of suboptimal therapy, 26% had anti-TNF dose escalation, 21% needed augmentation with non-biologic therapy, 9% underwent UC-related surgery and 29% discontinued their index anti-TNF. Of those who discontinued index anti-TNF (N = 156), 58% switched to another anti-TNF therapy. Conclusion In this large multinational cohort, more than 60% of UC patients had ≥1 indicator of suboptimal anti-TNF therapy. Predominant indicators included dose escalation and discontinuation of anti-TNF therapy. Disclosure of Interest J. Lindsay Grant/research support from: MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, Consultant for: MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, Speaker bureau with: MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, J. Gisbert Grant/research support from: MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, Consultant for: MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, Speaker bureau with: MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, R. Mody Employee of: Takeda Pharmaceuticals International, Inc, L. Peyrin-Biroulet Consultant for: Abbvie, MSD, Jansse, Takeda, Hospira, Celltrion, Biogaran, Speaker bureau with: Abbvie, MSD, Janssen, Takeda, Mitsubishi, A. Armuzzi Grant/research support from: MSD, Consultant for: Abbvie, Hospira, Liily, MSD, Mundipharma, Pfizer, Sofar, Takeda, Speaker bureau with: Abbvie, Astra-Zeneca, Chiesi, Ferring, Hospira, MSD, Otsuka, Takeda, Zambon, B. Bokemeyer Grant/research support from: Abbvie, Ferring, UCB, Consultant for: Abbvie, MSD, Shire, Ferring, UCB, Hospira, Takeda, Movetis, Speaker bureau with: Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB, G. Nguyen Consultant for: Janssen and Abbvie, J. Siebenaler Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., O. Akerborg Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., M. Smyth Employee of: Takeda Development Centre Europe Ltd, London, UK

With ubiquitous mobile computing devices spreading throughout the urban environment of everyday life, there is a growing need to better understand person-place relationships and how technology can play a role in this urban experience. To this end, we propose a mobile methodology called Walking & Talking, an observed walking tour with participants through the city, which makes it easy and motivating for them to discuss their personal relationships with a place. The paper will describe a case study where the method was successfully applied to elicit rich, contextualized and intimate data, making it a useful research tool for the fields of urban interaction design and mobile & location aware technology.

The increase in information gathered and processed by large-scale urban sensors networks has generated a corresponding rise in interest in information visualization and interaction design. Creative initiatives in urban space explore how to translate complex data streams into engaging and meaningful outputs for experiencing and interacting with information. This one-day workshop will bring together practitioners and researchers who are interested in the organisation of human activities in urban space, and how these can be supported by technology in a positive way. This event is intended to share and stimulate an interdisciplinary discussion on the topic, with a view to contributing towards more consistent and creative forms of experiencing urban information.

We have used synthetic peptide antibodies to probe conformational changes that occur during the cleavage cascade which generates the capsid proteins of a picornavirus. The initial translation product of 97 kDa, the precursor of all four structural proteins, is cleaved to form a 63 kDa fragment which, we show, has significantly different folding characteristics to both its larger parent and its products. We demonstrate that proteolytic cleavages as distant as 520 residues from epitopes confer sufficiently large conformational changes as to render them unrecognisable. To our knowledge, this is the first demonstration of this phenomenon in the picornavirus system.

Interaction Design, in an urban context, is an increasingly important field of research. City populations are currently in a state of rapid flux. Conurbations are fast becoming a hybrid of the physical environment and the digital datasphere. How we, as physical beings, will connect with, interpret and adapt this increasing dataflow residing in our cities is already becoming a significant research question. The SIG organisers will frame the discussion through a human–centred view of the concerns, experiences and behaviours that may occur in cities of the future. By adopting an approach of Thinking and Doing it is hoped that the SIG will act as a catalyst for community building.

Evaluates how economic co‐operation can be organized for the mutual advantage of the two economies of Northern Ireland and the Republic of Ireland. The methodological approach adopted by the authors explores the dynamics of market design within the two transitional economies and examines how they could contribute to the performance of an all‐island economy. The emphasis is on public utilities, electricity and telecommunications as sources of inter‐firm synergies. At a time when many European countries are moving towards greater integration, it is imperative that the two economies on the island of Ireland integrate in order to realize competitive advantages. Integration may not be the panacea for solving specific economic problems such as unemployment or housing shortages, however, it will solve the problem of diseconomies of small scale which impair the competitiveness of commercially oriented public utility firms on the island. The politics is not about the spoils of a united Ireland but the gains from participation in an integrated Europe. The primary objective is in realizing the economic reality of all‐island commercial activities which will dissipate rents, eliminate inefficiencies, create incentives and release real economic growth.

Introduction Crohn’s disease (CD) patients treated with tumour necrosis factor antagonists (anti-TNFs) may require therapy changes over time, which may be considered as indicators of suboptimal therapy. Methods A multi-national, multicentre, retrospective, chart review study was conducted to assess the indicators of suboptimal therapy among adult CD patients receiving their first anti-TNF [infliximab (IFX) or adalimumab (ADA)] between June 2009 and June 2011 (index therapy). The indicators of suboptimal therapy during 2 year follow up were: anti-TNF dose-escalation (assessed >4 months after index to allow for initial dose adjustments), augmentation with a non-biologic drug, discontinuation of first anti-TNF, switching to another anti-TNF and CD-related surgery. The percentages of patients with each indicator type and ≥1 indicator by country for each anti-TNF drug are summarised descriptively. Results The study included 657 CD patients with mean age (SD) of 39.2 (13.2) years, 51% females, 51% with moderate to severe CD at index, 44% and 56% on ADA and IFX, respectively and 71% on combination therapy with a non-biologic drug. Overall, 56% of CD patients had ≥1 indicator of suboptimal therapy, 20% of patients had dose escalation, 18% needed augmentation with a non-biologic, 29% discontinued first anti-TNF, and 17% underwent a CD-related surgery. Of those who discontinued (N = 183), 70% switched to another anti-TNF. Conclusion In this large multi-national cohort, over half of the CD patients had ≥1 indicator of anti-TNF suboptimal therapy. Predominant indicators included dose escalation, discontinuation and switching to another anti-TNF. Disclosure of Interest A. Armuzzi Grant/research support from: MSD, Consultant for: Abbvie, Hospira, Liily, MSD, Mundipharma, Pfizer, Sofar, Takeda, Speaker bureau with: Abbvie, Astra-Zeneca, Chiesi, Ferring, Hospira, MSD, Otsuka, Takeda, Zambon, J. Lindsay Grant/research support from: MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, Consultant for: MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, Speaker bureau with: MSD, Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts, R. Mody Employee of: Takeda Pharmaceuticals International, Inc, B. Bokemeyer Grant/research support from: Abbvie, Ferring, UCB, Consultant for: Abbvie, MSD, Shire, Ferring, UCB, Hospira, Takeda, Movetis, Speaker bureau with: Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB, J. Gisbert Grant/research support from: MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, Consultant for: MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, Speaker bureau with: MSD, Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma, L. Peyrin-Biroulet Consultant for: Abbvie, MSD, Jansse, Takeda, Hospira, Celltrion, Biogaran, Speaker bureau with: Abbvie, MSD, Janssen, Takeda, Mitsubishi, G. Nguyen Consultant for: Janssen and Abbvie, J. Siebenaler Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., O. Akerborg Conflict with: Employee of Mapi, a company hired to conduct the study by Takeda Pharmaceuticals International, Inc., M. Smyth Employee of: Takeda Development Centre Europe Ltd, London, UK

Introduction Corticosteroids (CS) can effectively induce remission of Crohn’s disease (CD), but serious side effects prohibit long-term use. Vedolizumab (VDZ) maintenance therapy resulted in a significantly higher percentage of patients with CS-free remission at week 52 versus placebo (PBO) in the GEMINI 2 study of moderately to severely active CD. 1 Methods In GEMINI 2, patients who responded to VDZ induction therapy at week 6 were re-randomised to PBO or VDZ for 46 weeks. From week 6 onward, patients with clinical response began a CS tapering regimen. With exploratory and post hoc analyses, we characterised CS dose reductions following VDZ therapy in the population of patients on stable CS doses (≤30 mg/day prednisone or equivalent) at baseline (week 0). Median CS dose over time, change from baseline CS dose, and CS-free status at week 52 were summarised overall and by tumour necrosis factor antagonist (anti-TNF) treatment (naive or failure) history. Results At week 52, 68% of patients with baseline CS use decreased their CS dose with VDZ treatment compared with 62% with PBO ( Table ). The median CS dose in either treatment group (VDZ or PBO) at week 52 was 5 mg/day. Higher percentages of patients (overall and anti-TNF-naive) required CS doses of ≤7.5 mg/day with VDZ versus PBO at week 52 ( Table ). In anti-TNF-naive patients, the median CS dose at week 52 was 2.7 mg/day with VDZ and 5.0 mg/day with PBO. At week 52, higher percentages of VDZ-treated patients were CS- free for 90 or 180 consecutive days than PBO-treated patients. Conclusion VDZ maintenance therapy was associated with numerically higher percentages of CS-free patients at week 52 and patients who were CS-free for 90 or 180 days than PBO. Interpretation of these post hoc analyses, including the degree of dose reduction, is limited by differing initiation weeks for CS tapering per patient and small sample sizes. Reference 1 Sandborn WJ, et al . N Engl J Med . 2013; 369 :711–721; NCT00783692 . Disclosure of Interest E. Loftus Jr Grant/research support from: AbbVie, Janssen, UCB, Takeda, Pfizer, GSK, Amgen, BMS, Genentech, Robarts Clinical Trials, Gilead, Receptos, Consultant for: AbbVie, Janssen, UCB, Takeda, Immune Pharmaceuticals, Celgene, MedImmune, Theradiag, Genentech, Seres Health, Sun Pharmaceuticals, BMS, C. Siegel Grant/research support from: AbbVie, Janssen, Salix, Takeda, UCB, Consultant for: AbbVie, Amgen, Janssen, Lilly, Pfizer, Takeda, UCB, Speaker bureau with: AbbVie, Janssen, Takeda, R. Panaccione Grant/research support from: Abbott, and UCB Inc, Consultant for: Abbott, Biogen, Axcan Pharma Inc, BMS, Centocor Inc, Chemocentryx, Ferring, Genentech Inc, Lippincott Williams & Wilkins, Medscape, Osiris Therapeutics, Inc, Novartis, Genentech Inc, Elan Pharmaceuticals, Inc, UCB, W. Sandborn Grant/research support from: Janssen, AbbVie, Pfizer, Amgen, Genentech, Consultant for: Janssen, AbbVie, Pfizer, Amgen, Genentech, Takeda, Speaker bureau with: AbbVie, Takeda, M. Smyth Employee of: Takeda Development Centre Europe Ltd, London, UK, A. James Employee of: Takeda Development Centre Europe Ltd, London, UK, J. Xu Employee of: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA, B. Abhyankar Employee of: Takeda Development Centre Europe Ltd, London, UK

Introduction The objective of this analysis was to examine the clinical and economic impact of vedolizumab (VDZ) compared with conventional therapy (CT) in the treatment of moderately to severely active ulcerative colitis (UC) in the UK (UK). Methods A Markov decision analytic model in Microsoft Excel was used to compare VDZ with CT (aminosalicylates, corticosteroids, immunomodulators) for the treatment of UC patients in the UK. We considered three populations: the overall intent-to-treat (ITT) population; anti-tumour necrosis factor (TNF)-naive patients; and patients who previously failed anti-TNF therapy from the GEMINI 1 trial. Population characteristics, efficacy data, and UC health-state utility data were obtained from the GEMINI 1 trial. Other inputs (e.g., unit costs, adverse event disutilities, probability of surgery, mortality) were obtained from published literature. Costs are presented in 2014 British pounds. Outcomes included quality-adjusted life-years (QALY), time spent in clinical response, and time spent in clinical remission. Time horizons included 10 year (base-case) and lifetime (scenario) horizons, with costs and outcomes discounted by 3.5% per year. Incremental cost-effectiveness ratios (ICER) were presented for VDZ compared with CT. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty, and a scenario analysis was explored using efficacy data from a network meta-analysis. Results Over the base-case (10 year) time horizon, the model predicted that patients on VDZ accrued more QALY than patients on CT: 5.551 QALY vs 5.397 QALY in the ITT population (ICER=£33,297/QALY); 5.597 vs 5.403 QALY for anti-TNF-naive patients (ICER=£24,657/QALY; network meta-analysis results: utilities 5.898 for VDZ vs 5.555 for CT and ICER=£4,862/QALY); and 5.463 vs 5.373 QALY for anti-TNF-failure patients (£64,999/QALY). Patients on VDZ spent more time in clinical response (0.99 years vs 0.27 years for the ITT population) and clinical remission (0.64 years vs 0.13 years) than patients on CT. Scenario analyses with a lifetime horizon showed VDZ to be even more cost-effective (ITT population ICER=£20,599/QALY). Sensitivity analyses suggest that results are most sensitive to treatment response and transition probabilities. Conclusion Our model predicted that treatment with VDZ improves QALY, increases time in remission and response, and is a cost-effective treatment option for both anti-TNF naive and anti-TNF failure patients with moderately to severely active UC compared with CT over 10 year and lifetime horizons. Disclosure of Interest M. Wilson Conflict with: Employee of RTI Health Solutions, a company hired to conduct the study by Takeda Pharmaceuticals, M. Kerrigan Conflict with: Employee of PHMR Ltd, a company hired to conduct the study by Takeda Pharmaceuticals, M. Smyth Employee of: Takeda Development Centre Europe Ltd, London, UK, H. Chevrou-Severac Employee of: Takeda Pharmaceuticals GmbH, Zurich, Switzerland, A. Bergman Employee of: Takeda Pharmaceuticals GmbH, Zurich, Switzerland, R. Selby Employee of: Takeda UK Ltd., Bucks, UK