bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and microbiological characteristics of Moraxella keratitis
Authors: McSwiney Terence Joseph , Knowles Susan J , Murphy Conor C
Published: February 2019

Background/aims

To describe the risk factors, clinical features, bacterial subspecies characteristics and treatment outcomes of Moraxella keratitis in a single centre.

Methods

A retrospective review of all patients diagnosed with Moraxella keratitis between November 2012 and December 2017 at the Royal Victoria Eye and Ear Hospital, Dublin, Ireland was performed. Matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry was used to identify Moraxella subspecies.

Results

Forty-one cases of Moraxella keratitis were identified. Previous ocular surgery and diabetes were the most common local and systemic risk factors. The most common appearance on presentation was an oval-shaped paracentral infiltrate with a mean diameter of 4.2 mm. Mean presenting and final logarithm of minimal angle of resolution visual acuity were 1.307±0.74 and 0.99±1.01, respectively. Surgical procedures, including penetrating keratoplasty, corneal glueing or evisceration, were required to manage nine (22%) patients. Mean time to complete corneal epithelialisation was 32 (range, 7–109) days and mean duration of topical antibiotic therapy was 54 (range, 9–124) days. MALDI-TOF analysis revealed the following Moraxella subspecies: nonliquifaciens (16; 39%), lacunata (15; 36%), osloensis (4; 10%) and catarrhalis (2; 5%). In four cases (10%), subspecies analysis was inconclusive. M.nonliquifaciens and M. lacunata were associated with larger infiltrates on presentation (p<0.05), required more surgical intervention and longer treatment duration (p<0.001).

Conclusion

In this large series of patients from Ireland, Moraxella keratitis was notable for its severity on presentation, slow response to antimicrobial therapy, high risk of surgical intervention and poor visual outcome. We have demonstrated the value of subspecies identification using MALDI-TOF by reporting significant differences in the clinical features and prognosis of M. nonliquifaciens and M. lacunata compared with other subspecies.
Which criteria are used to clear patients to return to sport after primary ACL reconstruction? A scoping review
Authors: Burgi Ciara R , Peters Scott , Ardern Clare L , Magill John R , Gomez Christina D , Sylvain Jonathan , Reiman Michael P
Published: February 2019

Objective

To describe the criteria used to clear athletes to return to sport (RTS) following primary ACL reconstruction.

Design

Scoping review.

Data sources

MEDLINE, Embase, CINAHL and SPORTDiscus electronic databases were searched using keywords related to ACL and RTS.

Eligibility criteria

Prospective or retrospective studies reporting at least one RTS criterion for athletes who had primary ACL reconstruction with an autograft.

Results

In total, 209 studies fulfilled the inclusion criteria. RTS criteria were categorised into six domains: time, strength, hop testing, clinical examination, patient-report and performance-based criteria. From the 209 included studies, time was used in 178 studies (85%), and in 88 studies (42%) was the sole RTS criterion. Strength tests were reported in 86 studies (41%). Sixteen different hop tests were used in 31 studies (15%). Clinical examination was used in 54 studies (26%), patient report in 26 studies (12%) and performance-based criteria in 41 studies (20%).

Time and impairment-based measures dominated RTS criteria, despite sport being a complex physical and biopsychosocial activity with demands across all aspects of function. Time was included as a criterion in 85% of studies, and over 80% of studies allowed RTS before 9 months. Whether RTS tests are valid—do they predict successful RTS?—is largely unknown.
Role for structured telephone clinics in paediatric gastroenterology: reflections, lessons and patient feedback
Authors: Duncan Hazel , Russell Richard K
Published: February 2019

Background

Telephone clinics have been established within our department to try and improve communication with families, limit waiting times and help face-to-face clinics run more efficiently. As part of the ongoing care needs for our patients and families it was felt important to determine if telephone clinics were meeting the needs of the young person and family as well as those of the health professional.

Objective

To assess the effects of a structured consultant delivered telephone clinic.

Method

Data were collected regarding patients who had a consultant telephone appointment between July 2016 and March 2017. Data collected include demographics and appointment reason. An evaluation questionnaire was sent to all parent/carer(s).

Results

25 clinics comprising 194 contacts, including 34 duplicate contacts. 120 questionnaires sent. 7/160 (4.3%) were new patients. The main contact reason was biopsy results after endoscopy (93/180; 52%). Failure to attend rate was significantly lower at 18/194 (9.2%) compared with failure to attend rate of 52/240 (21.6%) for a traditional clinic (p<0.001). 40/120 (33%) returned completed questionnaires, 25/40 (68.4%) reported the reason for appointment was test results. Travel time and school attendance were identified as main advantages. Mean parental rating score for the service was 8/10 with 21/40 (54%) scoring the service as 10/10.

Conclusion

The initial results of this audit are promising. Structured telephone appointments have a key role in delivering patient care in paediatric gastroenterology and have benefits to health professional, parent/carer and patients. These clinics have now been widely adopted by all members of our department.
Genetic polymorphisms in tumour necrosis factor receptors (TNFRSF1A/1B) illustrate differential treatment response to TNFα inhibitors in patients with Crohn’s disease
Authors: Qasem Ahmad , Ramesh Seela , Naser Saleh A
Published: February 2019

Background﻿

Monoclonal antibodies inhibiting tumour necrosis factor-α (TNFα) signalling pathway (anti-TNFα) have been widely used in Crohn’s disease (CD). However, treatment response varies among patients with CD and the clinical outcome is dependent on single nucleotide polymorphisms (SNP) in TNFα receptor superfamily 1A and 1B (TNFRSF1A/1B).

Methods

We tested nine SNPs inTNFα, TNFRSF1AandTNFRSF1Bby TaqMan genotyping from peripheral blood samples of 104 subjects. Additionally, we quantified the effects of these SNPs on their corresponding gene expression by RT-PCR and susceptibility toMycobacterium aviumsubspparatuberculosis(MAP) infection byIS900nested PCR.

Results

Four SNPs (TNFα:rs1800629, TNFRSF1A:rs767455, TNFRSF1B:rs1061624andTNFRSF1B:rs3397) were over-represented significantly (p<0.05) among patients with CD compared with healthy controls. TheTNFRSF1A:rs767455GG genotype was found in 15/54 patients with CD (28%), while it was only found in 2/50 healthy controls (4%) (OR 9.2, 95% CI 1.98 to 42.83). TheTNFRSF1B:rs3397TT genotype was found in 15/54 patients with CD (28%) compared with (4/50) healthy controls (8%) (OR 4.4, 95% CI 1.36 to 14.14). Furthermore, the SNPsTNFRSF1A:rs767455andTNFRSF1B:rs3397were associated with downregulating their corresponding genes significantly (p<0.05). MAP infection was predominantly found among patients with CD in comparison to healthy controls (57% vs 8%, respectively), which was also dependent on the SNPsTNFRSF1A:rs767455andTNFRSF1B:rs3397. Our SNP haplotype analysis ofTNFRSF1A:rs767455andTNFRSF1B:rs3397indicates that the G–T haplotype is significantly distributed among patients with CD (46%) and MAP infection susceptibility is also associated with this specific haplotype (31%).

Conclusion

The SNPsTNFRSF1A:rs767455andTNFRSF1B:rs3397,which are known to affect anti-TNFα clinical outcome in CD, were associated with lower corresponding gene expression and higher MAP infection susceptibility.
Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel
Authors: Pate Jennifer , Gutierrez Juilo A , Frenette Catherine T , Goel Aparna , Kumar Sonal , Manch Richard A , Mena Edward A , Pockros Paul J , Satapathy Sanjaya K , Yimam Kidist K , Gish Robert G
Published: February 2019

Background and aims

This article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.

Methods

In May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.

Results

These recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.

Conclusions

Pruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.
Mutational load may predict risk of progression in patients with Barrett’s oesophagus and indefinite for dysplasia: a pilot study
Authors: Trindade Arvind J , McKinley Matthew J , Alshelleh Mohammad , Levi Gabriel , Stewart Molly , Quinn Kathy J , Thomas Rebecca M
Published: February 2019

Background and aims

Mutational load (ML) has been shown to help risk-stratify those that may progress from non-dysplastic Barrett’s oesophagus (BE) to dysplastic disease. Management of patients with BE and indefinite for dysplasia (BE-IND) is challenging and risk stratification tools are lacking. The aim of this pilot study is to evaluate the utility of ML for risk stratification in patients with BE-IND.

Methods

This is a single-centre, retrospective pilot study evaluating ML quantification in patients with BE-IND. Histology at follow-up endoscopy at least 1 year after the baseline endoscopy was used to determine if a patient progressed to low or high dysplasia. The ML levels were then compared among patients who progressed to dysplasia versus those who did not.

Results

Thirty-five patients who met the inclusion criteria were identified, and seven met the exclusion criteria. Twenty-eight patients were analysed, of whom eight progressed to low-grade dysplasia (6) and high-grade dysplasia (2). Seven of these eight patients had some level of genomic instability detected in their IND biopsy (ML ≥0.5). Ten of the 20 (50%) who did not progress had no ML level. At an ML cut-off above 1.5, the risk of progression to high-grade dysplasia was 33% vs 0% (p=0.005), with a sensitivity of 100% and a specificity of 85%.

Conclusion

These results indicate that ML may be able to risk-stratify progression to high-grade dysplasia in BE-IND. Larger studies are needed to confirm these findings.
Can propensity score matching be applied to cross-sectional data to evaluate Community-Based Rehabilitation? Results of a survey implementing the WHO’s Community-Based Rehabilitation indicators in Vietnam
Authors: Mason Catherine , Sabariego Carla , Thắng Đoàn Mạnh , Weber Jörg
Published: February 2019

Objectives

Community-Based Rehabilitation (CBR) is a multi-sectoral approach working to equalise opportunities and include people with disabilities in all aspects of life. The complexity of CBR and often limited resources lead to challenges when attempting to quantify its effectiveness, with randomisation and longitudinal data rarely possible. Statistical methods, such as propensity score matching (PSM), offer an alternative approach to evaluate a treatment when randomisation is not feasible. The aim of this study is to examine whether PSM can be an effective method to facilitate evaluations of results in CBR when data are cross-sectional.

Design

Cross-sectional survey.

Setting and participants

Data were collected using the WHO’s CBR Indicators in Vietnam, with treatment assignment (participating in CBR or not) determined by province of residence. 298 participants were selected through government records.

Results

PSM was conducted using one-to-one nearest neighbour method on 10 covariates. In the unmatched sample, significant differences between groups were found for six of the 10 covariates. PSM successfully adjusted for bias in all covariates in the matched sample (74 matched pairs). A paired t-test compared the outcome of ‘community inclusion’ (a score based on selected indicators) between CBR and non-CBR participants for both the matched and unmatched samples, with CBR participants found to have significantly worse community inclusion scores (mean=17.86, SD=6.30, 95% CI 16.45 to 19.32) than non-CBR participants (mean=20.93, SD=6.16, 95% CI 19.50 to 22.35); t(73)=3.068, p=0.001. This result did not differ between the matched and unmatched samples.

Conclusion

PSM successfully reduced bias between groups, though its application did not affect the tested outcome. PSM should be considered when analysing cross-sectional CBR data, especially for international comparisons where differences between populations may be greater.
Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis
Authors: Donnan Jennifer R , Grandy Catherine A , Chibrikov Eugene , Marra Carlo A , Aubrey-Bassler Kris , Johnston Karissa , Swab Michelle , Hache Jenna , Curnew Daniel , Nguyen Hai , Gamble John-Michael
Published: February 2019

Objective

To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies.

Design

We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs).

Intervention

SGLT2 inhibitors, compared with placebo or active comparators.

Primary outcomes

Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations.

Results

We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I2=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I2=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I2=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I2=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I2=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture.

Conclusions

Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear.

PROSPERO registration number

CRD42016038715.
Qualitative study to elicit patients’ and primary care physicians’ perspectives on the use of a self-management mobile health application for knee osteoarthritis
Authors: Barber Tanya , Sharif Behnam , Teare Sylvia , Miller Jean , Shewchuk Brittany , Green Lee A , Marlett Nancy , Cibere Jolanda , Mrklas Kelly , Wasylak Tracy , Li Linda C , Campbell-Scherer Denise , Marshall Deborah A
Published: February 2019

Objective

To elicit perspectives of family physicians and patients with knee osteoarthritis (KOA) on KOA, its treatment/management and the use of a mobile health application (app) to help patients self-manage their KOA.

Design

A qualitative study using Cognitive Task Analysis for physician interviews and peer-to-peer semistructured interviews for patients according to the Patient and Community Engagement Research (PaCER) method.

Setting

Primary care practices and patient researchers at an academic centre in Southern Alberta.

Participants

Intentional sampling of family physicians (n=4; 75% women) and patients with KOA who had taken part in previous PaCER studies and had experienced knee pain on most days of the month at any time in the past (n=5; 60% women).

Results

Physician and patient views about KOA were starkly contrasting. Patient participants expressed that KOA seriously impacted their lives and lifestyles, and they wanted their knee pain to be considered as important as other health problems. In contrast, physicians uniformly conceptualised KOA as a relatively minor health problem, although they still recognised it as a painful condition that often limits patients’ activities. Consequently, physicians did not regard KOA as a condition to be proactively and aggressively managed. The gap between physicians’ and patients’ conceptualisation of KOA and its treatment extended to the use of an app for self-management. While patients were supportive of the app, physicians were sceptical of its use and focused more on accountability and patient resources.

Conclusions

The clear discord between physicians’ mental models and patients’ lived experience and perceived needs around KOA emphasised a gap in understanding and communication about treatment and management of KOA. As such, this preliminary and formative research will inform a codesign approach to develop an app that will act as a communications tool between patients and physicians, enabling patient–physician discussions regarding modifiable self-management options based on a patient’s perspectives and needs.
Evaluation of the intensive outpatient clinic: study protocol for a prospective study of high-cost, high-need patients in the University of Utah Health system
Authors: Bannon Brittany L , Lucier Michelle , Fagerlin Angela , Kim Jaewhan , Kiraly Bernadette , Weir Peter , Ozanne Elissa M
Published: February 2019

Introduction

The University of Utah (UofU) Health intensive outpatient clinic (IOC) is a primary care clinic for medically complex (high-cost, high-need) patients with Medicaid. The clinic consists of a multidisciplinary care team aimed at providing coordinated, comprehensive and patient-centred care. The protocol outlines the quantitative design of an evaluation study to determine the IOC’s effects on reducing healthcare utilisation and costs, as well as improving patient-reported health outcomes and quality of care.

Methods and analysis

High-risk patients, with high utilisation and multiple chronic illnesses, were identified in the Medicaid ACO population managed by the UofU Health plans for IOC eligibility. A prospective, case-control study design is being used to match 100 IOC patients to 200 control patients (receiving usual care within the UofU) based on demographics, health utilisation and medical complexity for evaluating the primary outcome of change in healthcare utilisation and costs. For the secondary outcomes of patient health and care quality, a prepost design will be used to examine within-person change across the 18 months of follow-up (ie, before and after IOC intervention). Logistic regression and hierarchical, longitudinal growth modelling are the two primary modelling approaches.

Ethics and dissemination

This work has received ethics approval by the UofU Institutional Review Board. Results from the evaluation of primary and secondary outcomes will be disseminated in scientific research journals and presented at national conferences.
Nurses’ 12-hour shifts and missed or delayed vital signs observations on hospital wards: retrospective observational study
Authors: Dall’Ora Chiara , Griffiths Peter , Redfern Oliver , Recio-Saucedo Alejandra , Meredith Paul , Ball Jane
Published: February 2019

Objectives

12-hour shifts worked by nurses on acute hospital wards have been associated with increased rates of missed care reported by nurses. This study aimed to measure the association between nurses working shifts of at least 12 hours and an objective measure of missed care: vital signs observations taken on time according to an acuity-based surveillance protocol.

Design

A retrospective observational study using routinely collected data from March 2012 to March 2015.

Setting

32 general inpatient wards at a large acute hospital in England.

Participants

658 628 nursing shifts nested in 24 069 ward days.

Outcome measures

The rate of daily delayed and missed vital signs observations. We focused on situations where vital signs observations were required at least every 4 hours and measured the number of instances where observations were delayed or missed, per 24-hour period. For each ward and each day, shift patterns were characterised in terms of proportion of care hours per patient day deriving from ‘long’ shifts (≥12 hours) for both registered nurses and healthcare assistants.

Results

On 99 043 occasions (53%), observations were significantly delayed, and on 81 568 occasions (44%), observations were missed. Observations were more likely to be delayed when a higher proportion of the hours worked by healthcare assistants were part of long shifts (IRR=1.05; 95% CI 1.00 to 1.10). No significant association was found in relation to the proportion of hours registered nurses worked as long shifts.

Conclusion

On days when a higher proportion of hours worked by healthcare assistants are from long shifts, the risk of delaying vital signs observations is higher, suggesting lower job performance. While longer shifts are thought to require fewer staff resources to maintain nurse-to-patient ratios, any benefits may be lost if staff become less productive.
Impact of point-of-care C reactive protein in ambulatory care: a systematic review and meta-analysis
Authors: Verbakel Jan Y , Lee Joseph J , Goyder Clare , Tan Pui San , Ananthakumar Thanusha , Turner Philip J , Hayward Gail , Van den Bruel Ann
Published: February 2019

Objective

The aim of this review was to collate all available evidence on the impact of point-of-care C reactive protein (CRP) testing on patient-relevant outcomes in children and adults in ambulatory care.

Design

This was a systematic review to identify controlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services. Ovid Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, DARE, Science Citation Index were searched from inception to March 2017.

Eligibility criteria for selecting studies

Controlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services, measuring a change in clinical care, including but not limited to antibiotic prescribing rate, reconsultation, clinical recovery, patient satisfaction, referral and additional tests. No language restrictions were applied.

Data extraction

Data were extracted on setting, date of study, a description of the intervention and control group, patient characteristics and results. Methodological quality of selected studies and assessment of potential bias was assessed independently by two authors using the Cochrane Risk of Bias tool.

Results

11 randomised controlled trials and 8 non-randomised controlled studies met the inclusion criteria, reporting on 16 064 patients. All included studies had a high risk of performance and selection bias. Compared with usual care, point-of-care CRP reduces immediate antibiotic prescribing (pooled risk ratio 0.81; 95% CI 0.71 to 0.92), however, at considerable heterogeneity (I2=72%). This effect increased when guidance on antibiotic prescribing relative to the CRP level was provided (risk ratios of 0.68; 95% CI 0.63 to 0.74 in adults and 0.56; 95% CI 0.33 to 0.95 in children). We found no significant effect of point-of-care CRP testing on patient satisfaction, clinical recovery, reconsultation, further testing and hospital admission.

Conclusions

Performing a point-of-care CRP test in ambulatory care accompanied by clinical guidance on interpretation reduces the immediate antibiotic prescribing in both adults and children. As yet, available evidence does not suggest an effect on other patient outcomes or healthcare processes.

PROSPERO registration number

CRD42016035426; Results.
Systematic scoping review protocol for clinical prediction rules (CPRs) in the management of patients with spinal cord injuries
Authors: Boggenpoel Blake , Madasa Vuyolwethu , Jeftha Tarryn , Joseph Conran
Published: February 2019

Introduction

The upsurge in the use of clinical prediction models in general medical practice is a result of evidence-based practice. However, the total number of clinical prediction rules (CPRs) currently being used or undergoing impact analysis in the management of patients who have sustained spinal cord injuries (SCIs) is unknown. This scoping review protocol will describe the current CPRs being used and highlight their possible strengths and weaknesses in SCI management.

Methods and analysis

Arksey and O’Malley’s scoping review framework will be used. The following databases will be searched to identify relevant literature relating to the use of CPRs in the management of patients who have sustained an SCI: PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), ScienceDirect, EBSCOhost, Medline, OvidMedline and Google Scholar. Grey literature as well as reference lists of included studies will be searched. All studies relating to the use of CPRs in the management of patients with SCIs will be included. Literature searches and data extraction will be performed independently by two groups of reviewers.

Ethics and dissemination

Ethical clearance is not required for this scoping review study since only secondary data sources will be used. The findings of this review will be disseminated by means of peer-reviewed publication and conference proceedings. The final paper will be submitted for publication. Results of this review will also be presented at relevant conferences and disseminated to important stakeholders such as practicing physicians within specialised spinal care facilities within South Africa.
Online tool for monitoring adverse events in patients with cancer during treatment (eRAPID): field testing in a clinical setting
Authors: Warrington Lorraine , Absolom Kate , Holch Patricia , Gibson Andrea , Clayton Beverly , Velikova Galina
Published: February 2019

Objectives

Electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is an online system developed to support patient care during cancer treatment by improving the detection and management of treatment-related symptoms. Patients can complete symptom reports from home and receive severity-based self-management advice, including notifications to contact the hospital for severe symptoms. Patient data are available in electronic records for staff to review. Prior to the commencement of a randomised controlled trial (RCT), field testing of the intervention was undertaken to troubleshoot practical issues with intervention integration in clinical practice.

Design

Observational clinical field testing.

Setting

Medical oncology breast service in a UK cancer centre.

Participants

12 patients receiving chemotherapy for early breast cancer and 10 health professionals (oncologists and specialist nurses).

Intervention

Patients were asked to use the eRAPID intervention and complete weekly online symptom reports during four cycles of chemotherapy. Clinical staff were invited to access and use patient data in clinical assessments.

Analysis

Descriptive data on the frequency of online symptom report completion and severe symptom notifications were collated. Verbal and written feedback was collected from patients and staff and semistructured interviews were conducted to explore patient experiences. Interviews were transcribed and analysed thematically.

Results

The testing ran from January 2014 to March 2014. Feedback from patients and staff was largely positive. Patients described eRAPID as ‘reassuring’ and ‘comforting’ and valued the tailored management advice. Several changes were made to refine eRAPID. In particular, improvement of the clinical notification, patient reminder systems and changes to patient and staff training.

Conclusions

The field testing generated valuable results used to guide refinement of eRAPID prior to formal intervention evaluation. Feedback indicated that eRAPID has the potential to improve patients’ self-efficacy, knowledge and confidence with managing symptoms during treatment. A large-scale RCT is underway with data collection due to finish in October 2018.
Assisted ventilation in motor neurone disease during inpatient palliative care: barriers and utilisation
Authors: Gleeson Aoife , Johnson Faye
Published: February 2019

Objectives

An increasing number of patients with motor neuron disease (MND) in the UK and Ireland use assisted ventilation, and a small proportion of these use long-term tracheostomy ventilation (TV).1 2 NICE guidelines recommend that patients with MND should routinely receive specialist palliative care input.3 The aim was to establish the extent to which hospices and specialist palliative care units (SPCUs) in the UK and Ireland currently manage patients with MND using assisted ventilation especially TV and to identify any associated barriers.

Methods

A 25-item questionnaire was developed in Survey Monkey. A link to the questionnaire was emailed to every medical director (n=185) of inpatient hospices/SPCUs in the UK and Ireland.

Results

The response rate was 42.4% (n=78). 97.4% of units admit patients with MND on non-invasive ventilation (NIV), but only 28.2% admit those using TV. 80.8% of units have adequate expertise in the management of NIV, compared with 7.7% for managing TV. 35.9% and 2.6% of units have a policy for managing patients using NIV and TV, respectively. 14.1% respondents had been involved in the care of patients with MND using TV, in the specialist palliative care setting in the last 5 years.

Conclusions

A minority of UK and Irish hospices/SPUs provide support to TV MND patients and few units currently have management or admission policies for this cohort of patients. Respondents indicated a lack of appropriate expertise and experience. Further exploration of these barriers is required to establish how to optimise care for TV MND patients in this setting.
British Society of Gastroenterology Endoscopy Quality Improvement Programme (BSG EQIP): Implementing new endoscopic techniques and technologies into clinical practice
Authors: Bhandari Pradeep , Subramaniam Sharmila , East James E
Published: February 2019

Endoscopy has rapidly evolved from a diagnostic modality to a therapeutic tool with the advent of new technologies (medical devices or imaging) and techniques (types of procedures). Although the rapid advancement of technology is welcomed, this can pose its own problems if there is no robust system in place to assess the safety and efficacy of new endoscopic devices or practices or guide its use among clinicians prior to adoption. This is unlike the rigorous process that medical drugs need to go through from preclinical to clinical phases of development, often with controlled trials being conducted prior to integration of a new drug into clinical practice. In this review, we will identify the problems related to implementation of new technologies and techniques as well as propose solutions. We will outline the use of comparative effectiveness studies as a model for assessing new technologies and provide a structured pathway to support clinicians in their endeavour to introduce new devices or procedures in their clinical practice safely. We will also discuss the role of the British Society of Gastroenterology in risk stratifying new techniques and supporting clinicians in setting up national registries, training and business case development. This review will provide a framework for improving the quality and safety of our current practice of implementing new endoscopic technologies and techniques in the National Health Service.
Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn’s disease: the LIR!C Trial
Authors: de Groof E Joline , Stevens Toer W , Eshuis Emma J , Gardenbroek Tjibbe J , Bosmans Judith E , van Dongen JM , Mol Bregje , Buskens Christianne J , Stokkers Pieter C F , Hart Ailsa , D’Haens Geert R , Bemelman Willem A , Ponsioen Cyriel Y
Published: February 2019

Objective

Evaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn’s disease failing conventional therapy.

Design

A multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn’s disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.

Results

In total, 143 patients were randomised. Mean Crohn’s disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €−8931; 95% CI €−12 087 to €−5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €−5729, 95% CI €−10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score.

Conclusion

Laparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.

Clinical trial registration number

Dutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).
RSPO2 gene rearrangement: a powerful driver of β-catenin activation in liver tumours
Authors: Longerich Thomas , Endris Volker , Neumann Olaf , Rempel Eugen , Kirchner Martina , Abadi Zahra , Uhrig Sebastian , Kriegsmann Mark , Weiss Karl Heinz , Breuhahn Kai , Mehrabi Arianeb , Weber Tim Frederik , Wilkens Ludwig , Straub Beate K , Rosenwald Andreas , Schulze Falko , Brors Benedikt , Froehling Stefan , Pellegrino Rossella , Budczies Jan , Schirmacher Peter , Stenzinger Albrecht
Published: February 2019

Objective

We aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC).

Design

Large cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed.

Results

A roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microdeletion on chromosome 8q23.1 was detected as a new morphomolecular driver of β-catenin-activated HCA. RSPO2 fusion positive HCA displayed upregulation of RSPO2 protein, nuclear accumulation of β-catenin and transcriptional activation of β-catenin-target genes indicating activation of Wingless-Type MMTV Integration Site Family (WNT) signalling. Architectural and cytological atypia as well as interstitial invasion indicated malignant transformation in one of the RSPO2 rearranged b-HCAs. The RSPO2 gene rearrangement was also observed in three β-catenin-activated HCCs developing in context of chronic liver disease. Mutations of the human telomerase reverse transcriptase promoter—known to drive malignant transformation of CTNNB1-mutated HCA—seem to be dispensable for RSPO2 rearranged HCA and HCC.

Conclusion

The RSPO2 gene rearrangement leads to oncogenic activation of the WNT signalling pathway in HCA and HCC, represents an alternative mechanism for the development of b-HCA and may drive malignant transformation without additional TERT promoter mutation.
Relevance of TP53 for CLL diagnostics
Authors: Catherwood Mark A , Gonzalez David , Donaldson David , Clifford Ruth , Mills Ken , Thornton Patrick
Published: February 2019

TP53disruption in chronic lymphocytic leukaemia (CLL) is a well-established prognostic marker and informs on the appropriate course of treatment for patients.TP53status is commonly assessed by fluorescence in situ hybridisation for del(17 p) and Sanger sequencing forTP53mutations. At present, current screening methods forTP53mutations fail to detect diagnostically relevant mutations potentially leading to inappropriate treatment decisions. In addition, low levels of mutations that are proving to be clinically relevant may not be discovered with current less sensitive techniques. This review describes the structure, function and regulation of the TP53 protein, the mutations found in cancer and CLL, the relevance ofTP53disruption in CLL and the current screening methods forTP53mutations including next-generation sequencing.
Socioeconomic inequality in drug reimbursement during end-of-life care: a nationwide study
Authors: Daugaard Cecilie , Neergaard Mette Asbjoern , Vestergaard Anne Høy Seeman , Nielsen Mette Kjærgaard , Johnsen Søren Paaske
Published: February 2019

Background

In Denmark, patients who are terminally ill have the right to drug reimbursement due to terminal illness (DRTI). DRTI, a proxy marker of planned end-of-life care, is intended to be equally accessible regardless of socioeconomic position. This study examined social and socioeconomic differences in DRTI among Danish patients who are terminally ill.

Methods

This cross-sectional study based on individual-level nationwide data included all patients dying from cancer, dementia, ischaemic heart disease, chronic obstructive pulmonary disease, chronic liver disease, congestive heart failure, diabetes or stroke in 2006–2015 (n=307 188). We analysed associations between social and socioeconomic position (education, income, cohabiting status, migrant status and employment) and DRTI. Prevalence ratios (PR) and 95% CIs were estimated using log-linear models adjusted for age, gender, comorbidity, cause of death and residence.

Results

Overall, 27.9% of patients received DRTI (n=85 616). A substantial difference in likelihood of receiving DRTI was observed among patients with a social and socioeconomic profile associated with the highest versus lowest probability of DRTI (adjusted PR 1.44, 95% CI 1.18 to 1.75). The probability of DRTI was higher among patients with high income compared with low income (adjusted PR 1.22, 95% CI 1.17 to 1.26). Also, living with a partner and being immigrant or descendant of such were associated with higher probability of DRTI compared with living alone and of Danish origin, whereas employment was associated with lower probability of DRTI compared with retirement.

Conclusion

Social and socioeconomic position was associated with the likelihood of receiving DRTI, which indicates that planned end-of-life care is not equally accessible in Denmark.
H2AFY promoter deletion causes PITX1 endoactivation and Liebenberg syndrome
Authors: Kragesteen Bjørt K , Brancati Francesco , Digilio Maria Cristina , Mundlos Stefan , Spielmann Malte
Published: February 2019

Background

Structural variants (SVs) affecting non-coding cis-regulatory elements are a common cause of congenital limb malformation. Yet, the functional interpretation of these non-coding variants remains challenging. The human Liebenberg syndrome is characterised by a partial transformation of the arms into legs and has been shown to be caused by SVs at the PITX1 locus leading to its misregulation in the forelimb by its native enhancer element Pen. This study aims to elucidate the genetic cause of an unsolved family with a mild form of Liebenberg syndrome and investigate the role of promoters in long-range gene regulation.

Methods

Here, we identify SVs by whole genome sequencing (WGS) and use CRISPR-Cas9 genome editing in transgenic mice to assign pathogenicity to the SVs.

Results

In this study, we used WGS in a family with three mildly affected individuals with Liebenberg syndrome and identified the smallest deletion described so far including the first non-coding exon of H2AFY. To functionally characterise the variant, we re-engineered the 8.5 kb deletion using CRISPR-Cas9 technology in the mouse and showed that the promoter of the housekeeping gene H2afy insulates the Pen enhancer from Pitx1 in forelimbs; its loss leads to misexpression of Pitx1 by the pan-limb activity of the Pen enhancer causing Liebenberg syndrome.

Conclusion

Our data indicate that housekeeping promoters may titrate promiscuous enhancer activity to ensure normal morphogenesis. The deletion of the H2AFY promoter as a cause of Liebenberg syndrome highlights this new mutational mechanism and its role in congenital disease.
Systematic review of prehospital haemostatic dressings
Authors: Welch Matthew , Barratt J , Peters A , Wright C
Published: February 2019

Introduction

Haemorrhage is one of the leading causes of battlefield and prehospital death. Haemostatic dressings are an effective method of limiting the extent of bleeding and are used by military forces extensively. A systematic review was conducted with the aim of collating the evidence on current haemostatic products and to assess whether one product was more effective than others.

Methods

A systematic search and assessment of the literature was conducted using 13 health research databases including MEDLINE and CINAHL, and a grey literature search. Two assessors independently screened the studies for eligibility and quality. English language studies using current-generation haemostatic dressings were included. Surgical studies, studies that did not include survival, initial haemostasis or rebleeding and those investigating products without prehospital potential were excluded.

Results

232 studies were initially found and, after applying exclusion criteria, 42 were included in the review. These studies included 31 animal studies and 11 clinical studies. The outcomes assessed were subject survival, initial haemostasis and rebleeding. A number of products were shown to be effective in stopping haemorrhage, with Celox, QuikClot Combat Gauze and HemCon being the most commonly used, and with no demonstrable difference in effectiveness.

Conclusions

There was a lack of high-quality clinical evidence with the majority of studies being conducted using a swine haemorrhage model. Iterations of three haemostatic dressings, Celox, HemCon and QuikClot, dominated the studies, probably because of their use by international military forces and all were shown to be effective in the arrest of haemorrhage.
20 Armoured Infantry Brigade downgrade study: epidemiology of principal conditions and plugging leaks in the rehabilitation pipeline
Authors: Papworth James , Osborne L , Shimmings M A , Roberts C C S
Published: February 2019

Introduction

In April 2017, 22% of Army Full-time Trade Trained Strength was downgraded, reducing fully deployable strength to 60 546, against a target of 82 000. In June 2017, Commander 20 Armoured Infantry Brigade (20 AI Bde) initiated a study to look at the principal conditions causing medical downgrading, as a stepping stone to finding ways of reducing injury, enhancing rehabilitation and improving deployability.

Method

The Defence Medical Information Capability Programme medical records for every downgraded soldier in 20 AI Bde and supporting units were scrutinised to identify their Medical Deployment Standard and the primary condition causing downgrading.

Results

A total of 842 downgraded soldiers were identified from a held strength of 3827 personnel. Sixty-five per cent of these downgrades were due to musculoskeletal injury (MSKI). Of this 65%, the majority were due to knee (31%), spine (28%) and foot/ankle (23%). Of the remaining 35%, the majority were due to noise-induced hearing loss (NIHL) (22%), adjustment disorders (19%) and non-freezing cold injury (NFCI) (13%).

Several factors that slowed an individual’s recovery pathway were identified. They mainly relate to soldiers being lost to follow-up through lack of active case management.

Conclusions

MSKI is responsible for most downgraded personnel at Brigade level. The distribution of principal conditions is similar to previous studies looking at recruits and individual units.

The creation of a rehabilitation troop, delivering active case management, can reduce the number of soldiers leaking out of the rehabilitation pipeline.
Using machine learning to optimize selection of elderly patients for endovascular thrombectomy
Authors: Alawieh Ali , Zaraket Fadi , Alawieh Mohamed Baker , Chatterjee Arindam Rano , Spiotta Alejandro
Published: February 2019

Background

Endovascular thrombectomy (ET) is the standard of care for treatment of acute ischemic stroke (AIS) secondary to large vessel occlusion. The elderly population has been under-represented in clinical trials on ET, and recent studies have reported higher morbidity and mortality in elderly patients than in their younger counterparts.

Objective

To use machine learning algorithms to develop a clinical decision support tool that can be used to select elderly patients for ET.

Methods

We used a retrospectively identified cohort of 110 patients undergoing ET for AIS at our institution to train a regression tree model that can predict 90-day modified Rankin Scale (mRS) scores. The identified algorithm, termed SPOT, was compared with other decision trees and regression models, and then validated using a prospective cohort of 36 patients.

Results

When predicting rates of functional independence at 90 days, SPOT showed a sensitivity of 89.36% and a specificity of 89.66% with an area under the receiver operating characteristic curve of 0.952. Performance of SPOT was significantly better than results obtained using National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT score, or patients’ baseline deficits. The negative predictive value for SPOT was >95%, and in patients who were SPOT-negative, we observed higher rates of symptomatic intracerebral hemorrhage after thrombectomy. With mRS scores prediction, the mean absolute error for SPOT was 0.82.

Conclusions

SPOT is designed to aid clinical decision of whether to undergo ET in elderly patients. Our data show that SPOT is a useful tool to determine which patients to exclude from ET, and has been implemented in an online calculator for public use.