Catheter-Associated Urinary Tract Infection (CAUTI) Prevention Strategy Using Education in an Intensive Care Unit (ICU)

Purpose: To measure clinical impact of an evidence-based educational strategy on urinary tract infection (UTI) rates in a 900+ bed acute care facility located in a southwestern state in the United States (US). Clinical Question: Will a focu son staff education in the ICU on proper placement techniques, care, and early removal of urinary retention catheters reduce incidences of CAUTIs in an ICU setting

Feasibility and acceptability of web-based enhanced relapse prevention for bipolar disorder (ERPonline):trial protocol

BACKGROUND: Relapse prevention interventions for Bipolar Disorder are effective but implementation in routine clinical services is poor. Web-based approaches offer a way to offer easily accessible access to evidence based interventions at low cost, and have been shown to be effective for other mood disorders. METHODS/DESIGN: This protocol describes the development and feasibility testing of the ERPonline web-based intervention using a single blind randomised controlled trial. Data will include the extent to which the site was used, detailed feedback from users about their experiences of the site, reported benefits and costs to mental health and wellbeing of users, and costs and savings to health services. We will gain an estimate of the likely effect size of ERPonline on a range of important outcomes including mood, functioning, quality of life and recovery. We will explore potential mechanisms of change, giving us a greater understanding of the underlying processes of change, and consequently how the site could be made more effective. We will be able to determine rates of recruitment and retention, and identify what factors could improve these rates. DISCUSSION: The findings will be used to improve the site in accordance with user needs, and inform the design of a large scale evaluation of the clinical and cost effectiveness of ERPonline. They will further contribute to the growing evidence base for web-based interventions designed to support people with mental health problems

Modeling photosynthetically active radiation from satellite-derived estimations over mainland Spain

A model based on the known high correlation between photosynthetically active radiation (PAR) and global horizontal irradiance (GHI) was implemented to estimate PAR from GHI measurements in this present study. The model has been developed using satellite-derived GHI and PAR estimations. Both variables can be estimated using Kato bands, provided by Satellite Application Facility on Climate Monitoring (CM-SAF), and its ratio may be used as the variable of interest in order to obtain the model. The study area, which was located in mainland Spain, has been split by cluster analysis into regions with similar behavior, according to this ratio. In each of these regions, a regression model estimating PAR from GHI has been developed. According to the analysis, two regions are distinguished in the study area. These regions belong to the two climates dominating the territory: an Oceanic climate on the northern edge; and a Mediterranean climate with hot summer in the rest of the study area. The models obtained for each region have been checked against the ground measurements, providing correlograms with determination coefficients higher than 0.99This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) [Project CGL2016-79284-P AEI/FEDER/UE]S

Factor IX Expression within the Normal Range Prevents Spontaneous Bleeds Requiring Treatment Following FLT180a Gene Therapy in Patients with Severe Hemophilia B: Long-Term Follow- up Study of the B-Amaze Program

Introduction: FLT180a (verbrinacogene setparvovec) is an investigational, liver-directed AAV gene therapy for the treatment of patients with hemophilia B (HB). FLT180a consists of a novel, potent, engineered capsid (AAVS3) containing an expression cassette encoding a Factor IX (FIX) gain-of-function protein variant ('Padua'; FIX-R338L). The B-AMAZE study was designed to identify a dose of FLT180a that maintains FIX activity within the normal range (50-150%) and thereby protect patients with severe HB from spontaneous and traumatic bleeds. Methods: B-AMAZE was a multicentre, open-label Phase 1/2 clinical trial (NCT03369444; sponsored by UCL) that evaluated FLT180a dose levels using an escalating/descending adaptive design in patients with severe (FIX activity <1%) or moderately severe (FIX activity 1-2%) HB who were negative for AAVS3 neutralizing antibodies. A novel regimen of prophylactic corticosteroids with/without tacrolimus was implemented to mitigate the impact of vector-related transaminitis on FIX expression. Patients who completed the 26-week B-AMAZE study were eligible for the ongoing long-term follow-up study (NCT03641703; sponsored by Freeline). Results: Ten HB patients received a single dose of FLT180a. Four FLT180a doses ranging from 3.84e11 vg/kg to 1.28e12 vg/kg were assessed. As of the data cut-off date, all patients have been followed for ≥16 months. FLT180a demonstrated a favorable safety profile, without evidence of inhibitors against FIX, infusion-related or allergic reactions. The most common treatment-related adverse event was transient elevation in alanine aminotransferase. An event of AV fistula thrombosis occurred in a 67-year-old patient who received the highest dose of 1.28e12 vg/kg (total dose of 1.15e14 vg) and had supranormal FIX levels; this patient was treated with anticoagulants. While these FIX levels demonstrate the potency of our proprietary AAVS3 capsid, this dose will not be used in future hemophilia studies. At Week 26 after FLT180a administration, a dose-response relationship was observed with mean FIX activity of 45.0%, 35.5%, 141.5%, and 175.5% for 3.84e11, 6.4e11, 8.32e11, and 1.28e12 vg/kg doses, respectively (Table); FIX activity levels ≥50% were achieved in 7 of 8 patients treated with the three highest doses. One patient (Patient 4) who received 6.4e11 vg/kg lost transgene expression early due to transaminitis and resumed routine factor prophylaxis. The 8.32e11 vg/kg cohort received an extended immune management regimen (9-18 weeks) with prophylactic tacrolimus in addition to prednisolone to prevent breakthrough vector-related transaminitis. However, after cessation of the immune management regimen, transaminitis with concomitant reductions in FIX activity was observed in all patients in the 8.32e11 vg/kg cohort. The combination of prophylactic tacrolimus and prednisolone appeared to have suppressed immune-mediated transaminitis while administered, but recurrence of transaminitis developed soon after cessation. This unique and previously unreported observation suggests that the longer-duration prophylactic immune management regimen may have prevented tolerization to the vector because this was not observed in earlier cohorts where a brief course of tacrolimus was given reactively for breakthrough transaminitis. All patients (including the 8.32e11 vg/kg cohort) have achieved steady state. Patients in the earliest cohort who received the lowest dose (3.84e11 vg/kg) have shown stable FIX activity for >3 years. There were no spontaneous bleeds that required FIX supplementation in patients who maintained FIX activity above 50%; Patient 4 in the 6.4e11 vg/kg cohort experienced two bleeds (cause unknown) after he lost transgene expression, which were treated with exogenous FIX. One patient received exogenous FIX for treatment of a traumatic bleed, but his FIX activity level was 57% at the time of the event. Additional efficacy and safety results with >3.5 years of follow-up will be presented. Conclusions: B-AMAZE is the first HB gene therapy study to achieve normal levels of FIX activity using relatively low vector doses. Results suggest that a dose of 7.7e11 vg/kg, coupled with a short course of prophylactic immune management, has the potential to achieve durable FIX activity in the normal range (50-150%) and thereby prevent spontaneous bleeds and normalize hemostasis in the event of traumatic bleeds

Feasibility and acceptability of integrated psychological therapy versus treatment as usual for people with bipolar disorder and co-morbid alcohol use:A single blind randomised controlled trial

Background Alcohol use is a common problem in bipolar disorder (BD) and evidence indicates more promising outcomes for alcohol use than other substances. No trials have evaluated individual integrated motivational interviewing and cognitive behaviour therapy (MI-CBT) for problematic alcohol use in BD. We therefore assessed the feasibility and acceptability of a novel MI-CBT intervention for alcohol use in BD. Methods A single blind RCT was conducted to compare MI-CBT plus treatment as usual (TAU) with TAU only. MI-CBT was delivered over 20 sessions with participants followed up at 3, 6, 9 and 12 months post-randomisation. Primary outcomes were the feasibility and acceptability of MI-CBT (recruitment to target, retention to follow-up and therapy, acceptability of therapy and absence of adverse events). We also conducted preliminary analyses of alcohol and mood outcomes (frequency and severity of alcohol use and time to mood relapse). Results 44 participants were recruited with 75% retention to 6 and 12 months follow-up. Therapy participants attended a mean of 17.6 (SD 4.5) sessions. Therapy alliance and treatment fidelity were acceptable. Qualitative interviews indicated the intervention was experienced as collaborative, and helpful, in addressing mood and alcohol issues, although risk of overconfidence following therapy was also identified. Clinical outcomes did not differ between arms at 12 months follow-up. Limitations As a feasibility and acceptability trial any secondary results should be treated with caution. Conclusions Integrated MI-CBT is feasible and acceptable, but lack of clinical impact, albeit in a feasibility study, suggests need for further development. Potential adaptations are discussed

Contemporary Art and Transitional Justice in Northern Ireland: The Consolation of Form

Abstract Contemporary artworks in Northern Ireland are explored here as critical constellations, in Walter Benjamin’s sense, that engage the cultural processes of transition through their problematisation of it. It is argued that the artworks become sites in which the assumptions of transition are opened up for critical reflection, requesting attention to the foreclosing of the meanings of memory, of past-and-future, of community. A mode of critical questioning of the present renders the present problematic not in terms of exclusions nor with reference to a past that cannot or will not be erased, but in terms of the present’s inability to be conceived through a linear conception of time. That is, the past and its relation to both the present and to the future are set in oscillation as artworks explore the complex temporalities of a present self-consciously attempting to narrate itself away from the past. The artworks, ‘without the bigotry of conviction’ as Seamus Deane put it, suggest that the task of dealing with the past is flawed wherever the past is conceived as a history that can be rendered present to be judged by subjects who are thereby placed beyond it. That is the illusion of a present ‘no-time’ that dovetails with the desires of commercial enterprise and neo-liberal conceptions of freedom. If this suggests an unceasing restlessness, the consolation is that this questioning does take a form, not as judgement or political decision but as artworks which by definition, remain open to reinterpretation and new understandings. These issues are discussed with reference to the work of four artists in Northern Ireland: the paintings of Rita Duffy, the photography and installation work of Anthony Haughey, and the sculptural works of Philip Napier and Mike Hogg

Improving access to psychological therapies (IAPT) for people with bipolar disorder:summary of outcomes from the IAPT demonstration site

Access to structured psychological therapy recommended for bipolar disorder (BD) is poor. The UK NHS Improving Access to Psychological Therapies initiative commissioned a demonstration site for BD to explore the outcomes of routine delivery of psychological therapy in clinical practice, which this report summarises. All clinically diagnosed patients with BD who wanted a psychological intervention and were not in acute mood episode were eligible. Patients were offered a 10-session group intervention (Mood on Track) which delivered NICE congruent care. Outcomes were evaluated using an open (uncontrolled), pre-post design. Access to psychological therapy increased compared to preceding 6 years by 54%. 202 people began treatment; 81% completed >5 sessions; median 9 sessions (range 6–11). Pre-post outcomes included personal recovery (primary outcome), quality of life, work and social functioning, mood and anxiety symptoms (secondary outcomes). Personal recovery significantly improved from pre to post-therapy; medium effect-size (d = 0.52). Secondary outcomes all improved (except mania symptoms) with smaller effect sizes (d = . 20–0.39). Patient satisfaction was high. Use of crisis services, and acute admissions were reduced compared to pre-treatment. It is possible to deliver group psychological therapy for bipolar disorder in a routine NHS setting. Improvements were observed in personal recovery, symptoms and wider functioning with high patient satisfaction and reduced service use

Effects of dose modifications on the safety and efficacy of dacomitinib for EGFR mutation-positive non-small-cell lung cancer

Aim: We evaluated reasons for dacomitinib dose reduction (DR) and examined adverse event (AE) incidence, key efficacy end points (progression-free survival [PFS]/overall survival [OS]), and pharmacokinetics in dose-reducing patients in the ARCHER 1050 trial. Patients & methods: Newly diagnosed patients with EGFR mutation-positive, advanced non-small-cell lung cancer received oral dacomitinib (45 mg once-daily [QD]), with stepwise toxicity-managing DR (30 and 15 mg QD) permitted. Results: Skin toxicities (62.7%) were the most common DR-leading AEs. The AE incidence and severity decreased following DRs. Initial plasma dacomitinib exposure (45 mg QD) was generally lower in patients remaining at 45 mg QD compared with dose-reducing patients. Median PFS and OS were similar in all dacomitinib-treated patients and dose-reducing patients. Conclusion: Tolerability-guided dose modifications enabled patients to continue with dacomitinib and benefit from PFS/OS improvement

Assessing feasibility and acceptability of web-based enhanced relapse prevention for bipolar disorder (ERPonline): a randomized controlled trial

Background: Interventions that teach people with Bipolar Disorder (BD) to recognise and respond to early warning signs of relapse are NICE recommended but implementation in clinical practice is poor. Objective: This study tests the feasibility and acceptability of a randomised controlled trial to evaluate an online enhanced relapse prevention intervention (ERPonline), and reports preliminary evidence of effectiveness. Methods: Single blind, parallel primarily online randomised controlled trial (n=96) over 48 weeks comparing ERPonline plus usual treatment to waitlist (WL) control plus usual treatment for people with BD recruited through National Health Services, voluntary organisations, and media. Randomisation was independent, minimised on number of previous episodes (<8,8-20,21+). Primary outcomes were feasibility and acceptability assessed by rates of study recruitment and retention, levels of intervention use, adverse events and participant feedback. Process and clinical outcomes were assessed by telephone and online and compared using linear models with intention-to-treat analysis. Results: Two hundred and eighty people registered interest online, from which ninety-six met inclusion criteria, consented and were randomised (49 to WL, 47 to ERPonline) over seventeen months, with 80% retention in telephone and online follow up, except week 48 online (76%). Acceptability was high for both ERPonline and trial methods. ERPonline cost approximately £19,340 to create, and £2176 per year to host and maintain the site. Qualitative data highlighted the importance of the relationship users have with online interventions and how this is created as an extension of the relationship with the humans perceived as offering and supporting its use. Differences between the group means suggested that access to ERPonline was associated with: a more positive model of bipolar disorder at 24 (10.70 (0.90-20.5 95%CIs)) and 48 weeks (13.1 (2.44-23.93 95%CIs)); increased monitoring of early warning signs of depression at 48 weeks (-1.39 (-2.61, -.163 95%CIs)) and of (hypo)mania at 24 (-1.72 (-2.98, -0.47 95%CIs)) and 48 weeks (-1.61 (-2.92, -0.30 95%CIs)), compared to WL. There was no evidence of impact of ERPonline on clinical outcomes or medication adherence, but relapse rates across both arms were very low (15%) and the sample remained high functioning throughout. One person died by suicide prior to randomisation. Five people in ERPonline and six in WL control reported ideas of suicide or self-harm during the study. None were deemed study related by an independent Trial Steering Committee. Conclusions: ERPonline offers a cheap accessible option for people seeking ongoing support following successful treatment. However, given high functioning and low relapse rates in this study, testing clinical effectiveness for this population would require very large sample sizes. Building in human support to use ERPonline should be considere

An exploratory randomised controlled trial of a web-based integrated bipolar parenting intervention (IBPI) for bipolar parents of young children (aged 3–10)

Background Communication, impulse control and motivation can all be affected by Bipolar Disorder (BD) making consistent parenting more difficult than for parents without mental health problems. Children of parents with BD (CPB) are at significantly increased risk of a range of mental health issues including Attention Deficit Hyperactivity Disorder (ADHD), anxiety, depression, substance use, and sleep disorders. Furthermore, CPB are also at elevated risk for BD compared to the general population. This paper describes the rationale and protocol for a pilot randomised controlled trial (RCT) designed to assess the feasibility and acceptability of a new online intervention providing interactive psychoeducational information and parenting support for parents with BD. Methods and design This article describes a single-blind randomised controlled trial comparing an Integrated Bipolar Parenting Intervention (IBPI) in addition to treatment as usual (TAU) with TAU alone. Participants will be recruited from across the UK from mental health services and through self-referral. The primary outcome of the study is the feasibility and acceptability of IBPI as indicated by recruitment to target, use of the intervention site, and retention to follow-up. Parents with BD allocated to the IBPI condition will have access to the intervention for 16 weeks. Effect size estimates will be obtained with respect to child behaviour, parenting skills and measures of parental mental health using measures taken at baseline (0), and at 16, 24, 36, and 48 weeks post randomization. Discussion This is the first randomised controlled trial of an integrated bipolar disorder parenting intervention. The benefits and challenges of delivering this online intervention, and evaluation using online RCT methodology are discussed. Trial registration Current Controlled Trials ISRCTN75279027 webcite Registered 12 August 201