bluuebunny/crossref_metadata_2025 huggingface dataset:
What shape do UK trainees want their training to be? Results of a cross-sectional study
Authors: Harries Rhiannon L , Rashid Mustafa , Smitham Peter , Vesey Alex , McGregor Richard , Scheeres Karl , Bailey Jon , Sohaib Syed Mohammed Afzal , Prior Matthew , Frost Jonathan , Al-Deeb Walid , Kugathasan Gana , Gokani Vimal J
Published: October 2016

Objectives

The British Government is acting on recommendations to overhaul postgraduate training to meet the needs of the changing population, to produce generalist doctors undergoing shorter broad-based training (Greenaway Review). Only 45 doctors in training were involved in the consultation process. This study aims to obtain a focused perspective on the proposed reforms by doctors in training from across specialities.

Design

Prospective, questionnaire-based cross-sectional study.

Setting/participants

Following validation, a 31-item electronic questionnaire was distributed via trainee organisations and Postgraduate Local Education and Training Board (LETB) mailing lists. Throughout the 10-week study period, the survey was publicised on several social media platforms.

Results

Of the 3603 demographically representative respondents, 69% knew about proposed changes. Of the respondents, 73% expressed a desire to specialise, with 54% keen to provide general emergency cover. A small proportion (12%) stated that current training pathway length is too long, although 86% felt that it is impossible to achieve independent practitioner-level proficiency in a shorter period of time than is currently required. Opinions regarding credentialing were mixed, but tended towards disagreement. The vast majority (97%) felt credentialing should not be funded by doctors in training. Respondents preferred longer placement lengths with increasing career progression. Doctors in training value early generalised training (65%), with suggestions for further improvement.

Conclusions

This is the first large-scale cross-specialty study regarding the Shape of Training Review. Although there are recommendations which trainees support, it is clear that one size does not fit all. Most trainees are keen to provide a specialist service on an emergency generalist background. Credentialing is a contentious issue; however, we believe removing aspects from curricula into post-Certificate of Completion of Training (CCT) credentialing programmes with shortened specialty training routes only degrades the current consultant expertise, and does not serve the population. Educational needs, not political winds, should drive changes in postgraduate medical education and all stakeholders should be involved.
Comparison of acupuncture pretreatment followed by letrozole versus letrozole alone on live birth in anovulatory infertile women with polycystic ovary syndrome: a study protocol for a randomised controlled trial
Authors: Li Juan , Ng Ernest Hung Yu , Stener-Victorin Elisabet , Hu Zhenxing , Wu Wanting , Lai Maohua , Wu Taixiang , Ma Hongxia
Published: October 2016

Introduction

The high prevalence of insulin resistance in women with polycystic ovary syndrome (PCOS) is considered to be one of the major pathophysiological changes in PCOS that leads to anovulatory infertility. We hypothesise that electroacupuncture pretreatment improves insulin sensitivity and leads to a higher ovulation rate and greater chances of live birth after the induction of ovulation. The effect of electroacupuncture pretreatment followed by ovulation induction in women with anovulatory PCOS has not been investigated before, and we present here a randomised controlled trial to test this hypothesis by comparing electroacupuncture pretreatment followed by letrozole versus letrozole alone in anovulatory women with PCOS.

Methods/analysis

This is a multicentre, randomised,and controlled trial. A total of 384 patients will be enrolled in this study and will be randomly allocated by a central randomisation system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo 16 weeks of electroacupuncture pretreatment followed by 4 cycles of letrozole, and the control group will only undergo 4 cycles of letrozole. The primary outcome will be the live birth rate. All statistical analyses will be performed using the SPSS program V.21.0 (SPSS, Chicago, Illinois, USA), and a p value <0.05 will be considered statistically significant.

Ethics/dissemination

This study has been approved by the ethics committees of each participating centre. Written consent will be obtained from each patient and her husband before any study procedure is performed. Adverse events will be categorised, and the percentage of patients experiencing adverse events or serious adverse events during the treatment period will be documented. The results of this trial will be disseminated in peer-reviewed journals and presented at international meetings.

Trial registration number

NCT02491333.
Educational disparities in the intention to quit smoking among male smokers in China: a cross-sectional survey on the explanations provided by the theory of planned behaviour
Authors: Droomers Mariël , Huang Xinyuan , Fu Wenjie , Yang Yong , Li Hong , Zheng Pinpin
Published: October 2016

Objectives

We aim to describe the intention to quit smoking among Chinese male smokers from different educational backgrounds and to explain this intention from their attitude, perceived social norms and self-efficacy regarding smoking cessation.

Setting

Participants were recruited from workplaces and communities to reflect the occupational distribution in three cities (Shanghai, Nanning and Mudanjiang) in China.

Design and participants

In 2013 interviews were conducted with 3676 male smokers aged 18 years and older.

Outcome measures

Multivariate logistic regression analyses calculated educational differences in the intention to quit smoking as well as the association between the intention to quit smoking and attitude, subjective norms, and self-efficacy. Bootstrapping estimated to what extent the educational disparities in the intention to quit smoking were mediated by these three determinants.

Results

No educational disparities in the intention to quit smoking within 1 or 6 months were observed among male Chinese smokers (p=0.623 and p=0.153, respectively). A less negative attitude, a higher perceived subjective norm towards smoking cessation, and a higher perceived self-efficacy to quit smoking were all associated with intention to quit (all p values <0.001). Perceived subjective norms were the only component of the theory of planned behaviour that statistically significantly mediated the differences in the intention to quit smoking (within 1 or 6 months) between the lowest educated Chinese men and the groups with lower (β=0.039, 95% CI 0.017 to 0.071 and β=0.043, 95% CI 0.019 to 0.073), higher (β=0.041, 95% CI 0.017 to 0.075 and β=0.045, 95% CI 0.019 to 0.077) and the highest education (β=0.045, 95% CI 0.019 to 0.080 and β=0.050, 95% CI 0.023 to 0.083).

Conclusions

In order to prevent future socioeconomic disparities in smoking cessation, investment in a more stimulating social environment and norms towards smoking cessation among particularly the lowest educated Chinese men is warranted.
Does the UKCAT predict performance on exit from medical school? A national cohort study
Authors: MacKenzie R K , Cleland J A , Ayansina D , Nicholson S
Published: October 2016

Objectives

Most UK medical programmes use aptitude tests during student selection, but large-scale studies of predictive validity are rare. This study assesses the UK Clinical Aptitude Test (UKCAT:http://www.ukcat.ac.uk), and 4 of its subscales, along with individual and contextual socioeconomic background factors, as predictors of performance during, and on exit from, medical school.

Methods

This was an observational study of 6294 medical students from 30 UK medical programmes who took the UKCAT from 2006 to 2008, for whom selection data from the UK Foundation Programme (UKFPO), the next stage of UK medical education training, were available in 2013. We included candidate demographics, UKCAT (cognitive domains; total scores), UKFPO Educational Performance Measure (EPM) and national exit situational judgement test (SJT). Multilevel modelling was used to assess relationships between variables, adjusting for confounders.

Results

The UKCAT—as a total score and in terms of the subtest scores—has significant predictive validity for performance on the UKFPO EPM and SJT. UKFPO performance was also affected positively by female gender, maturity, white ethnicity and coming from a higher social class area at the time of application to medical school An inverse pattern was seen for a contextual measure of school, with those attending fee-paying schools performing significantly more weakly on the EPM decile, the EPM total and the total UKFPO score, but not the SJT, than those attending other types of school.

Conclusions

This large-scale study, the first to link 2 national databases—UKCAT and UKFPO, has shown that UKCAT is a predictor of medical school outcome. The data provide modest supportive evidence for the UKCAT's role in student selection. The conflicting relationships of socioeconomic contextual measures (area and school) with outcome adds to wider debates about the limitations of these measures, and indicates the need for further research.
Healthcare costs in chronic kidney disease and renal replacement therapy: a population-based cohort study in Sweden
Authors: Eriksson Jonas K , Neovius Martin , Jacobson Stefan H , Elinder Carl-Gustaf , Hylander Britta
Published: October 2016

Objective

To compare healthcare costs in chronic kidney disease (CKD) stage 4 or 5 not on dialysis (estimated glomerular filtration rate <30 mL/min/1.73m2), peritoneal dialysis, haemodialysis and in transplanted patients with matched general population comparators.

Design

Population-based cohort study.

Setting

Swedish national healthcare system.

Participants

Prevalent adult patients with CKD 4 or 5 (n=1046, mean age 68 years), on peritoneal dialysis (n=101; 64 years), on haemodialysis (n=460; 65 years) and with renal transplants (n=825; 52 years) were identified in Stockholm County clinical quality registers for renal disease on 1 January 2010. 5 general population comparators from the same county were matched to each patient by age, sex and index year.

Primary and secondary outcome measures

Annual healthcare costs in 2009 incurred through inpatient and hospital-based outpatient care and dispensed prescription drugs ascertained from nationwide healthcare registers. Secondary outcomes were annual number of hospital days and outpatient care visits.

Results

Patients on haemodialysis had the highest mean annual cost (€87 600), which was 1.49 (95% CI 1.38 to 1.60) times that observed in peritoneal dialysis (€58 600). The mean annual cost was considerably lower in transplanted patients (€15 500) and in the CKD group (€9600). In patients on haemodialysis, outpatient care costs made up more than two-thirds (€62 500) of the total, while costs related to fluids ($29 900) was the largest cost component in patients on peritoneal dialysis (51%). Compared with their matched general population comparators, the mean annual cost (95% CI) in patients on haemodialysis, peritoneal dialysis, transplanted patients and patients with CKD was 45 (39 to 51), 29 (22 to 37), 11 (10 to 13) and 4.0 (3.6 to 4.5) times higher, respectively.

Conclusions

The mean annual costs were ∼50% higher in patients on haemodialysis than in those on peritoneal dialysis. Compared with the general population, costs were substantially elevated in all groups, from 4-fold in patients with CKD to 11, 29 and 45 times higher in transplanted patients and patients on peritoneal dialysis and haemodialysis, respectively.
Combination with intravenous iron supplementation or doubling erythropoietin dose for patients with chemotherapy-induced anaemia inadequately responsive to initial erythropoietin treatment alone: study protocol for a randomised controlled trial
Authors: Chen Lin , Jiang Hong , Gao Wei , Tu Ye , Zhou Ying , Li Xi , Zhu Zhe , Jiang Qixin , Zhan Haifeng , Yu Jiangming , Fu Chuangang , Gao Yong
Published: October 2016

Introduction

Erythropoietin (EPO) is a commonly used option in the treatment of chemotherapy-induced anaemia (CIA). However, ∼30–50% of patients fail to achieve an adequate response after initial treatment. Prior studies have demonstrated that intravenous iron might synergistically improve therapeutic response to EPO treatment in this patient population.

Methods and analysis

We will perform this multicentre, randomised, open-label, parallel-group, active controlled non-inferiority study to compare the two combination therapies of EPO plus intravenous iron regimen versus doubling the dose of EPO in patients with CIA who have an inadequate response to initial EPO treatment at a routine dose. A total of 603 patients with an increase in haemoglobin (Hb) <1 g/dL will be enrolled and randomised to one of the three study treatment groups at a 1:1:1 ratioGroup 1: EPO treatment at the original dose plus intravenous iron dextran 200 mg every 3 weeks (Q3W) for 15 weeks;Group 2: EPO treatment at the original dose plus intravenous iron dextran 100 mg, twice a week for 5 weeks;Group 3: the control group, doubling the EPO dose without preplanned iron supplementation. The primary outcome measure to compare is the Hb response rate at week 15 and the secondary end points involve therapeutic blood transfusions. Time-to-progression, adverse events and quality of life will also be evaluated.

Ethics and dissemination

All participants will provide informed consent; the study protocol has been approved by the independent ethics committee of Shanghai East Hospital. This study would clearly demonstrate the potential benefit of combining epoetin treatment with intravenous iron supplementation. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of CIA in China.

Trial registration number

NCT02731378.
Long-term cost-effectiveness of collaborative care (vs usual care) for people with depression and comorbid diabetes or cardiovascular disease: a Markov model informed by the COINCIDE randomised controlled trial
Authors: Camacho Elizabeth M , Ntais Dionysios , Coventry Peter , Bower Peter , Lovell Karina , Chew-Graham Carolyn , Baguley Clare , Gask Linda , Dickens Chris , Davies Linda M
Published: October 2016

Objectives

To evaluate the long-term cost-effectiveness of collaborative care (vs usual care) for treating depression in patients with diabetes and/or coronary heart disease (CHD).

Setting

36 primary care general practices in North West England.

Participants

387 participants completed baseline assessment (collaborative care: 191; usual care: 196) and full or partial 4-month follow-up data were captured for 350 (collaborative care: 170; usual care: 180). 62% of participants were male, 14% were non-white. Participants were aged ≥18 years, listed on a Quality and Outcomes Framework register for CHD and/or type 1 or 2 diabetes mellitus, with persistent depressive symptoms. Patients with psychosis or type I/II bipolar disorder, actively suicidal, in receipt of services for substance misuse, or already in receipt of psychological therapy for depression were excluded.

Intervention

Collaborative care consisted of evidence-based low-intensity psychological treatments, delivered over 3 months and case management by a practice nurse and a Psychological Well Being Practitioner.

Outcome measures

As planned, the primary measure of cost-effectiveness was the incremental cost-effectiveness ratio (cost per quality-adjusted life year (QALY)). A Markov model was constructed to extrapolate the trial results from short-term to long-term (24 months).

Results

The mean cost per participant of collaborative care was £317 (95% CI 284 to 350). Over 24 months, it was estimated that collaborative care was associated with greater healthcare usage costs (net cost £674 (95% CI −30 953 to 38 853)) and QALYs (net QALY gain 0.04 (95% CI −0.46 to 0.54)) than usual care, resulting in a cost per QALY gained of £16 123, and a likelihood of being cost-effective of 0.54 (willingness to pay threshold of £20 000).

Conclusions

Collaborative care is a potentially cost-effective long-term treatment for depression in patients with comorbid physical and mental illness. The estimated cost per QALY gained was below the threshold recommended by English decision-makers. Further, long-term primary research is needed to address uncertainty associated with estimates of cost-effectiveness.

Trial registration number

ISRCTN80309252; Post-results.
Non-inferiority trials: are they inferior? A systematic review of reporting in major medical journals
Authors: Rehal Sunita , Morris Tim P , Fielding Katherine , Carpenter James R , Phillips Patrick P J
Published: October 2016

Objective

To assess the adequacy of reporting of non-inferiority trials alongside the consistency and utility of current recommended analyses and guidelines.

Design

Review of randomised clinical trials that used a non-inferiority design published between January 2010 and May 2015 in medical journals that had an impact factor >10 (JAMA Internal Medicine,Archives Internal Medicine,PLOS Medicine,Annals of Internal Medicine,BMJ,JAMA,LancetandNew England Journal of Medicine).

Data sources

Ovid (MEDLINE).

Methods

We searched for non-inferiority trials and assessed the following: choice of non-inferiority margin and justification of margin; power and significance level for sample size; patient population used and how this was defined; any missing data methods used and assumptions declared and any sensitivity analyses used.

Results

A total of 168 trial publications were included. Most trials concluded non-inferiority (132; 79%). The non-inferiority margin was reported for 98% (164), but less than half reported any justification for the margin (77; 46%). While most chose two different analyses (91; 54%) the most common being intention-to-treat (ITT) or modified ITT and per-protocol, a large number of articles only chose to conduct and report one analysis (65; 39%), most commonly the ITT analysis. There was lack of clarity or inconsistency between the type I error rate and corresponding CIs for 73 (43%) articles. Missing data were rarely considered with (99; 59%) not declaring whether imputation techniques were used.

Conclusions

Reporting and conduct of non-inferiority trials is inconsistent and does not follow the recommendations in available statistical guidelines, which are not wholly consistent themselves. Authors should clearly describe the methods used and provide clear descriptions of and justifications for their design and primary analysis. Failure to do this risks misleading conclusions being drawn, with consequent effects on clinical practice.
Hyaluronic Acid Binding Sperm Selection for assisted reproduction treatment (HABSelect): study protocol for a multicentre randomised controlled trial
Authors: Witt K D , Beresford L , Bhattacharya S , Brian K , Coomarasamy A , Hooper R , Kirkman-Brown J , Khalaf Y , Lewis S E , Pacey A , Pavitt S , West R , Miller D
Published: October 2016

Introduction

The selection of a sperm with good genomic integrity is an important consideration for improving intracytoplasmic sperm injection (ICSI) outcome. Current convention selects sperm by vigour and morphology, but preliminary evidence suggests selection based on hyaluronic acid binding may be beneficial. The aim of the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial is to determine the efficacy of hyaluronic acid (HA)-selection of sperm versus conventionally selected sperm prior to ICSI on live birth rate (LBR). The mechanistic aim is to assess whether and how the chromatin state of HA-selected sperm corresponds with clinical outcomes—clinical pregnancy rate (CPR), LBR and pregnancy loss (PL).

Methods and analysis

Couples attending UK Centres will be approached, eligibility screening performed and informed consent sought. Randomisation will occur within 24 hours prior to ICSI treatment. Participants will be randomly allocated 1:1 to the intervention arm (physiological intracytoplasmic sperm injection, PICSI) versus the control arm using conventional methods (ICSI). The primary clinical outcome is LBR ≥37 weeks' gestation with the mechanistic study determining LBR's relationship with sperm DNA integrity. Secondary outcomes will determine this for CPR and PL. Only embryologists performing the procedure will be aware of the treatment allocation. Steps will be taken to militate against biases arising from embryologists being non-blinded. Randomisation will use a minimisation algorithm to balance for key prognostic variables. The trial is powered to detect a 5% difference (24–29%: p=0.05) in LBR ≥37 weeks' gestation. Selected residual sperm samples will be tested by one or more assays of DNA integrity.

Ethics and dissemination

HABSelect is a UK NIHR-EME funded study (reg no 11/14/34; IRAS REF. 13/YH/0162). The trial was designed in partnership with patient and public involvement to help maximise patient benefits. Trial findings will be reported as per CONSORT guidelines and will be made available in lay language via the trial web site (http://www.habselect.org.uk/).

Trial registration number

ISRCTN99214271; Pre-results.
Standardised tobacco packaging: a health policy case study of corporate conflict expansion and adaptation
Authors: Hatchard Jenny L , Fooks Gary J , Gilmore Anna B
Published: October 2016

Objectives

To investigate opposition to standardised tobacco packaging in the UK. To increase understanding of how transnational corporations are adapting to changes in their access to policymakers precipitated by Article 5.3 of the Framework Convention on Tobacco Control (FCTC).

Design

Case study web-based documentary analysis, using NVivo V.10. Examination of relationships between opponents of standardised packaging and transnational tobacco companies (TTCs) and of the volume, nature, transparency and timing of their activities.

Setting

UK standardised packaging policy debate 2011–2013.

Participants

Organisations selected on basis of opposition to, or facilitation thereof, standardised tobacco packaging in the UK; 422 associated documents.

Results

Excluding tobacco manufacturing and packaging companies (n=12), 109 organisations were involved in opposing standardised packaging, 82 (75%) of which had a financial relationship with 1 or more TTC. These 82 organisations (43 actively opposing the measure, 39 facilitating opposition) were responsible for 60% of the 404 activities identified, including the majority of public communications and research production. TTCs were directly responsible for 28% of total activities, predominantly direct lobbying, but also financially underwrote third party research, communication, mass recruitment and lobbying. Active organisations rarely reported any financial relationship with TTCs when undertaking opposition activities.

Conclusions

The multifaceted opposition to standardised packaging was primarily undertaken by third parties with financial relationships with major tobacco manufacturers. Low levels of transparency regarding these links created a misleading impression of diverse and widespread opposition. Countries should strengthen implementation of Article 5.3 of the FCTC by systematically requiring conflict of interest declarations from all organisations participating in political or media debates on tobacco control.
The iBRA-2 (immediate breast reconstruction and adjuvant therapy audit) study: protocol for a prospective national multicentre cohort study to evaluate the impact of immediate breast reconstruction on the delivery of adjuvant therapy
Authors: Dave Rajiv , O'Connell Rachel , Rattay Tim , Tolkien Zoe , Barnes Nicola , Skillman Joanna , Williamson Paula , Conroy Elizabeth , Gardiner Matthew , Harnett Adrian , O'Brien Ciara , Blazeby Jane , Potter Shelley , Holcombe Chris
Published: October 2016

Introduction

Immediate breast reconstruction (IBR) is routinely offered to improve quality of life for women with breast cancer requiring a mastectomy, but there are concerns that more complex surgery may delay the delivery of adjuvant oncological treatments and compromise long-term oncological outcomes. High-quality evidence, however, is lacking. iBRA-2 is a national prospective multicentre cohort study that aims to investigate the effect of IBR on the delivery of adjuvant therapy.

Methods and analysis

Breast and plastic surgery centres in the UK performing mastectomy with or without (±) IBR will be invited to participate in the study through the trainee research collaborative network. All women undergoing mastectomy ± IBR for breast cancer between 1 July and 31 December 2016 will be included. Patient demographics, operative, oncological and complication data will be collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR will be compared to determine the impact that IBR has on the time of delivery of adjuvant therapy. Prospective data on 3000 patients from ∼50 centres are anticipated.

Ethics and dissemination

Research ethics approval is not required for this study. This has been confirmed using the online Health Research Authority decision tool. This novel study will explore whether IBR impacts the time to delivery of adjuvant therapy. The study will provide valuable information to help patients and surgeons make more informed decisions about their surgical options. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative (MFAC) and the Reconstructive Surgery Trials Network (RSTN), the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS). Participating units will have access to their own data and collective results will be presented at relevant surgical conferences and published in appropriate peer-reviewed journals.
Assessment of proximal pulmonary arterial stiffness using magnetic resonance imaging: effects of technique, age and exercise
Authors: Weir-McCall Jonathan R , Kamalasanan Anu , Cassidy Deidre B , Struthers Allan D , Lipworth Brian J , Houston J Graeme
Published: October 2016

Introduction

To compare the reproducibility of pulmonary pulse wave velocity (PWV) techniques, and the effects of age and exercise on these.

Methods

10 young healthy volunteers (YHV) and 20 older healthy volunteers (OHV) with no cardiac or lung condition were recruited. High temporal resolution phase contrast sequences were performed through the main pulmonary arteries (MPAs), right pulmonary arteries (RPAs) and left pulmonary arteries (LPAs), while high spatial resolution sequences were obtained through the MPA. YHV underwent 2 MRIs 6 months apart with the sequences repeated during exercise. OHV underwent an MRI scan with on-table repetition. PWV was calculated using the transit time (TT) and flow area techniques (QA). 3 methods for calculating QA PWV were compared.

Results

PWV did not differ between the two age groups (YHV 2.4±0.3/ms, OHV 2.9±0.2/ms, p=0.1). Using a high temporal resolution sequence through the RPA using the QA accounting for wave reflections yielded consistently better within-scan, interscan, intraobserver and interobserver reproducibility. Exercise did not result in a change in either TT PWV (mean (95% CI) of the differences: −0.42 (−1.2 to 0.4), p=0.24) or QA PWV (mean (95% CI) of the differences: 0.10 (−0.5 to 0.9), p=0.49) despite a significant rise in heart rate (65±2 to 87±3, p<0.0001), blood pressure (113/68 to 130/84, p<0.0001) and cardiac output (5.4±0.4 to 6.7±0.6 L/min, p=0.004).

Conclusions

QA PWV performed through the RPA using a high temporal resolution sequence accounting for wave reflections yields the most reproducible measurements of pulmonary PWV.
Effect of vedolizumab (anti-α4β7-integrin) therapy on histological healing and mucosal gene expression in patients with UC
Authors: Arijs Ingrid , De Hertogh Gert , Lemmens Bart , Van Lommel Leentje , de Bruyn Magali , Vanhove Wiebe , Cleynen Isabelle , Machiels Kathleen , Ferrante Marc , Schuit Frans , Van Assche Gert , Rutgeerts Paul , Vermeire Severine
Published: October 2016

Objective

Lymphocyte recruitment to the inflamed gut is increased in UC. Inhibition of this cell trafficking by vedolizumab (VDZ) was successful in inducing and maintaining remission and in induction of endoscopic mucosal healing. There are no data on histological healing with VDZ. We studied histological changes following VDZ therapy and compared gene expression in patients with UC before and after therapy.

Design

Forty-one patients with UC from GEMINI I and LTS were studied before and at three time points (weeks 6/12/52) following VDZ therapy. Colonic biopsies were scored using the Geboes index and correlated with Mayo endoscopic subscore. Gene expression was analysed using Affymetrix gene arrays.

Results

Fifty-five per cent of patients achieving endoscopic healing (= Mayo endoscopic subscore 0–1) with VDZ at the studied time points also had histological healing (= Geboes grade 0–1). In most healers, some residual histological changes (eg, disturbed architecture and increased mononuclear cell infiltrate) were still observed, although this was less at week 52. VDZ restored expression of many inflammatory genes in patients with endoscopic healing only at week 52 and not before. In VDZ healers, the expression of many genes remained dysregulated at weeks 6/12/52 compared with controls.

Conclusions

VDZ induces histological healing in >50% of patients with endoscopic healing, with maximal effect at week 52. VDZ also restored, although incompletely, the colonic expression of many immune-related genes in patients with UC achieving endoscopic healing at week 52. However, persistent histological and gene dysregulations did remain even in healers, suggesting that maintenance therapy will be necessary to control the intestinal inflammation.

Trial registration numbers:

NCT00783718 and NCT00790933; post-results.
Dissenting from care.data: an analysis of opt-out forms
Authors: Vezyridis Paraskevas , Timmons Stephen
Published: October 2016

Background

Care.data was a programme of work led by NHS England for the extraction of patient-identifiable and coded information from general practitioner (GP) records for secondary uses. This study analyses the forms (on the websites of GP practices) which enabled patients to opt out.

Methods

Theoretical sampling and summative content analysis were used to collect and analyse dissent forms used by patients to opt out from care.data. Domains included basic information about the programme, types of objections and personal details required for identification purposes.

Results

One hundred opt-out forms were analysed. Fifty-four forms mentioned that this programme was run by NHS England. 81 forms provided two types of objections to data-sharing, and 15 provided only one objection. Only 26 forms mentioned that direct care would not be affected and 32 that patients maintain their right to opt back anytime. All but one of the opt-out forms we reviewed requested the name of the person wishing to opt out. 94 required a date of birth and 33 an NHS number. 82 required an address, 42 a telephone number and 7 an email address.

Conclusions

Numbers of patients (not) opting out should be treated with caution, because the variability of information provided and the varied options for dissent may have caused confusion among patients. To ensure that dissent is in accordance with individual preferences and moral values, we recommend that well-designed information material and standardised opt-out forms be developed for such data-sharing initiatives.
Effectiveness and safety of TNF inhibitors in adults with juvenile idiopathic arthritis
Authors: Kearsley-Fleet Lianne , McErlane Flora , Foster Helen E , Lunt Mark , Watson Kath D , Symmons Deborah P M , Hyrich Kimme L
Published: October 2016

Introduction

Many children with juvenile idiopathic arthritis (JIA) continue to have active disease into adulthood. Adults with JIA are a heterogeneous group, and the effects of tumour necrosis factor inhibitor (TNFi) therapies are not well described. This analysis aims to describe treatment outcomes among patients with JIA starting TNFi for the first time in adulthood.

Methods

Patients with arthritis onset <16 years starting their first TNFi therapy were identified from the British Society of Rheumatology Biologics Register. Disease activity outcomes (using 28-joint Disease Activity Score (DAS28) and Health Assessment Questionnaire (HAQ)) are presented at 1 year after start of therapy according to disease pattern. Incidence rates (IR) of adverse events per 1000 person-years (pyrs) were calculated. Outcomes in patients with polyarticular JIA were compared with a cohort (weighted for age and gender) of patients with rheumatoid arthritis (RA).

Results

In 443 adults with JIA starting a first TNFi, disease activity over 1 year improved across all measures. There were 58 first serious infections (IR 22.3/1000 pyrs); 4 cardiovascular events (IR 1.4/1000 pyrs); 11 uveitis events (IR 4.0/1000 pyrs) and 16 malignancies (IR 3.9/1000 pyrs). Compared with the weighted RA cohort, disease activity improvement was similar; malignancy rates were lower and uveitis rates much higher. While crude IR were similar, JIA patients had a lower risk of serious infection (HR 0.5 (95% CI 0.3 to 0.9)).

Conclusions

This is the largest study to describe disease activity and safety outcomes in adults with JIA receiving TNFi. Disease activity improved after 1 year in all disease patterns, suggesting TNFi is an effective therapy in this population.
Validation of risk scoring models for predicting stroke-associated pneumonia in patients with ischaemic stroke
Authors: Gong Siyin , Zhou Zhiwei , Zhou Muke , Lei Zhao , Guo Jian , Chen Ning , He Li
Published: October 2016

Objective

Various risk scoring models have been developed to predict stroke-associated pneumonia (SAP). We aim to determine whether these risk models could effectively predict SAP in Chinese patients with ischaemic stroke (IS).

Methods

Consecutive patients with IS in West China hospital between January 2011 and September 2013 were included to assess the predictive performance of risk scoring models, including Chumbler's score, A2DS2and AISAPS. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of each risk model in predicting pneumonia.

Results

A total of 1569 consecutive patients with IS within 30 days of onset in West China hospital were included. The incidence of pneumonia is 15.3%. The AUROC of Chumbler's score, A2DS2and AISAPS was 0.659, 0.728 and 0.758, respectively, and AISAPS had the highest AUROC.

Conclusions

A2DS2and AISAPS had acceptable discriminatory abilities to predict SAP in Chinese patients with IS within 30 days of onset.
Electrochemotherapy as a single treatment or adjuvant treatment to surgery of cutaneous sarcoid tumours in horses: a 31‐case retrospective study
Authors: Tozon N. , Kramaric P. , Kos Kadunc V. , Sersa G. , Cemazar M.
Published: October 2016

The aim of our study was to evaluate the efficacy of electrochemotherapy (ECT) with cisplatin as a single or adjuvant treatment for sarcoids in equids. Different treatment options with different success rates were proposed. Thirty‐one horses and one donkey with different clinical type, size and location of tumours were treated with ECT as a single treatment (18 animals with 52 tumour nodules) or as adjuvant treatment with marginal surgical excision (14 animals with 18 tumour nodules). In animals treated only with ECT with cisplatin, complete response was obtained in 48/52 (92.3 per cent) nodules and partial response in the other 4 nodules (7.7 per cent). In most cases, one to three sessions, only in two cases four and in one case five sessions, every 4 weeks were needed to obtain the measurable response. During the observation time, only in one case was the recurrence noted 60 months after treatment. Complete response in all 18 tumour nodules treated with surgery and adjuvant ECT was obtained and only one recurrence was noted after 14 months during the observation time. The results of this study show that ECT with cisplatin is an effective, safe, and simple local treatment of sarcoids in equids. According to the tumour size and location, single or combined treatment should be performed.
Enzymatic synthesis of 5-amino quinoline oligomers and evaluation of their free radical scavenging activity
Authors: Bilici Ali , Geçibesler İbrahim Halil , Kaya İsmet
Published: October 2016

The compound 5-aminoquinoline (AQ) was treated with horseradish peroxidase (HRP) and H2O2 in a reaction medium containing a dioxane:phosphate buffer mixture (70:30). Products (OAQ) with a degree of polymerization ranging from 4 to 12 were obtained. 1H NMR, FTIR, UV–vis, SEM, TG–DTA, DSC, XRD analysis, and conductivity measurements were conducted for characterization of OAQ. Compared with a monomer, OAQ showed higher thermal stability. After heating to 1000 °C, 46% of the initial weight of the OAQ remained. The antioxidant efficiencies of the monomer and oligomer were evaluated by the typical spectrophotometric method such as the bleaching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. OAQ showed improved DPPH activity compared with the AQ monomer.
Controls on the apex location of large deltas
Authors: Hartley Adrian J. , Weissmann Gary S. , Scuderi Louis
Published: October 2016

The majority of sediment transport to the world's oceans is routed via large deltas. We examine controls on delta apex location using a database of 84 of the world's largest deltas. Of the dataset, 94% of apices are controlled by either bedrock valleys (80%) or Pleistocene alluvial valleys (14%), suggesting that the principal control on modern apex development is valley exit and/or bedslope-mediated avulsion and not hydrodynamic backwater length. Valley exit control on large delta apex location may have been as important in the rock record as it is today, and should be considered as a key control on delta development.

Supplementary material
: Tabulated data on backwater length and apex type for studied deltas available at
https://doi.org/10.6084/m9.figshare.c.3469770
Slip preference analysis of faulting driven by strike-slip Andersonian stress regimes: an alternative explanation of the Rhodope metamorphic core complex (northern Greece)
Authors: Tranos Markos D.
Published: October 2016

Slip preference analysis (SPA) is accomplished by examining fault activation driven by different Andersonian strike-slip stress regimes. Strike-slip regimes favour the activation of strike-slip faults striking as high as 45° from the trend of the
σ
1
axis, thus favouring the predominance of R shears over P shears in a strike-slip shear zone. Reverse and normal faults cannot be activated simultaneously by a common strike-slip stress regime, and their activations depend on the stress ratio. The SPA provides new constraints on stress inversion methods that take into account only the misfit angle minimization criteria. Insights from the SPA give rise to an alternative explanation of the origin of the Tertiary Rhodope metamorphic core complex exposed in the inner part of the Hellenic orogen, which attributes the activation of the associated extensional shear zones and detachments to an Andersonian, transpression–strike-slip (TRP–SS) to strike-slip (SS) stress regime, and not to an extensional one as widely assumed. The variation from TRP–SS to SS is critical for the activation of the extensional structures and is attributed to the local and at-depth increase of the vertical crustal stresses owing to the ascent and emplacement of large plutonic bodies.
The Donkerhuk batholith, Namibia: A giant S-type granite emplaced in the mid crust, in a fore-arc setting
Authors: Clemens J. D. , Buick I. S. , Kisters A. F. M.
Published: October 2016

The mainly S-type Donkerhuk batholith intruded the accretionary prism in the Pan-African Damara Belt of Namibia. The batholith is elongate parallel to the regional SW–NE structural grain and the Okahandja Lineament Zone, which forms the accretionary prism backstop and the magma feeder zone. Over 5000 km
3
of granitic magmas were emplaced as thousands of sheets, over perhaps 20 myr, with sheet orientations determined by the regional stress field and wall-rock anisotropies. Some of the magma source rocks are inferred to have been cordierite-bearing, suggesting an upper pressure limit of 600 MPa (6 kbar). Calculated phase relations suggest magma emplacement at 450 MPa (4.5 kbar), corroborated by pseudosection modelling of the phase assemblage in a migmatitic wall rock. The magmas were initially highly H
2
O-undersaturated and at around 850°C, indicating fluid-absent conditions in the source rocks. This suggests intraplating of mantle magmas to provide heat and that the granitic magmas ascended only to the mid crust. The late-tectonic emplacement in a fore-arc shares similarities with younger and similarly large batholiths such as the Cretaceous Kodiak batholith in Alaska, but the internal architecture and age structure of the batholiths differ markedly, suggesting that different processes can trigger voluminous near-trench plutonism.

Supplementary material:
A Microsoft Excel spreadsheet, in xlsx format, showing the analytical data relevant to this paper, is available at
https://doi.org/10.6084/m9.figshare.c.3470880
Coal architecture, high-resolution correlation and connectivity: new insights from the Walloon Subgroup in the Surat Basin of SE Queensland, Australia
Authors: Morris Jennifer R. , Martin Mike A.
Published: October 2016

The Middle Jurassic (Aalenian–Oxfordian) Walloon Coal Measures are the focus of major coal seam gas projects in the Surat Basin, SE Australia. The ever-growing abundance of well data linked with ongoing coal seam gas exploitation has provided an opportunity to investigate coal body lateral extents and their associated geometries. From 120 wells over a 67.4 km
2
area, 25 coal horizons were correlated establishing a local coal seam area–thickness relationship. Individual plies (coal beds) average less than 30 cm and seams reach up to 10 m thick. In this heterogeneous succession, it is evident that coal correlation does not necessarily equate to coal continuity/connectivity as coal quality locally degrades from coal- to clay-rich facies. During a QGC Pty Ltd gas storage pilot test, offset well pressure response to gas injection provided evidence for coal connectivity and local faulting. By studying the relationships of the coals and interrelated facies, fluctuations in field-scale (local) accommodation space generation can be recognized. These intuitively convey information about the scale of the coal bodies, their possible correlatability and, ultimately, their connectivity. The presented methodology – specifically, the generation of areal extent v. thickness graphs and maps of coal heterogeneity – could be carried out in other basins to better understand the variability in coal body lateral extent, geometry and connectivity (connected permeability). In the context of this coal seam gas project, our workflow can be a useful tool for static reservoir characterization and selection of optimal well spacing; suggestions that it may also be useful for dynamic characterization will require further studies to assess.
Depositional environment and age determination of oils and condensates from the Barents Sea
Authors: Lerch Benedikt , Karlsen Dag Arild , Seland Reinert , Backer-Owe Kristian
Published: October 2016

The Barents Sea hosts multiple source rocks from Palaeozoic to Cretaceous age. Attempts in the past to link individual oil and condensates directly to one type of source rock have often been complicated due to ‘blended-oil’ signatures. As a result of uplift, remigration, alteration and mixing of petroleums, deconvolution of primary petroleum signatures in terms of maturity, age and depositional environment is generally complicated. In this paper, we use δ
13
C isotopes, and age- and source-related biomarkers to line out the main basin-scale trends concerning the depositional environments and source-rock ages, as well as the type of organic matter input that constitutes the inferred source-rock kerogen. Multivariate statistical analysis was applied as an auxillary tool to suggest petroleum families. Results classify the petroleums into four families: (1) Permian–Triassic-sourced petroleums; (2) Carboniferous-sourced petroleums; (3) Jurassic-sourced petroleums; and (4) phase-fractionated condensates charged from late mature Triassic–Jurassic source rocks. The inferred palaeo-environments for the petroleums cover marine, transitional and terrestrial depositional environments, and display geological variations that prevailed during Permian–Jurassic times. Isotope signatures and age-specific parameters suggest that many oils in the region should be considered as blends or mixtures derived from more than one source rock.
Heart-lung interaction in a model of COPD: importance of lung volume and direct ventricular interaction
Authors: Cheyne William S. , Williams Alexandra M. , Harper Megan I. , Eves Neil D.
Published: October 2016

Chronic obstructive pulmonary disease (COPD) is associated with dynamic lung hyperinflation (DH), increased pulmonary vascular resistance (PVR), and large increases in negative intrathoracic pressure (nITP). The individual and interactive effect of these stressors on left ventricular (LV) filling, emptying, and geometry and the role of direct ventricular interaction (DVI) in mediating these interactions have not been fully elucidated. Twenty healthy subjects were exposed to the following stressors alone and in combination: 1) inspiratory resistive loading of −20 cmH2O (nITP), 2) expiratory resistive loading to cause dynamic hyperinflation (DH), and 3) normobaric-hypoxia to increase PVR (hPVR). LV volumes and geometry were assessed using triplane echocardiography. LV stroke volume (LVSV) was reduced during nITP by 7 ± 7% (mean ± SD; P < 0.001) through a 4 ± 5% reduction in LV end-diastolic volume (LVEDV) ( P = 0.002), while DH reduced LVSV by 12 ± 13% ( P = 0.001) due to a 9 ± 10% reduction in LVEDV ( P < 0.001). The combination of nITP and DH (nITP+DH) caused larger reductions in LVSV (16 ± 16%, P < 0.001) and LVEDV (12 ± 10%, P < 0.001) than nITP alone ( P < 0.05). The addition of hPVR to nITP+DH did not further reduce LV volumes. Significant septal flattening (indicating DVI) occurred in all conditions, with a significantly greater leftward septal shift occurring with nITP+DH than either condition alone ( P < 0.05). In summary, the interaction of nITP and DH reduces LV filling through DVI. However, DH may be more detrimental to LV hemodynamics than nITP, likely due to mediastinal constraint of the heart amplifying DVI.