bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the PACT Resources Framework to Understand the Needs of Geriatric Primary Care Teams
Authors: Solimeo Samantha L. , Steffen Melissa J.A. , Gardner Ellen E. , Adjognon Omonyêlé , Shin Marlena H. , Moye Jennifer , Sullivan Jennifer L.
Published: May 2020

OBJECTIVES

To identify the perceived organizational resources required by healthcare workers to deliver geriatric primary care in a geriatric patient aligned care team (GeriPACT).

DESIGN

Cross‐sectional observational study using deductive analyses of qualitative interviews conducted with GeriPACT team members.

SETTING

GeriPACTs practicing at eight geographically dispersed Department of Veterans Affairs (VA) healthcare systems.

PARTICIPANTS

GeriPACT clinicians, nurses, clerical associates, clinical pharmacists, and social workers (n = 67).

MEASUREMENTS

Semistructured qualitative interviews conducted in person, transcribed, and then analyzed using the PACT Resources Framework.

RESULTS

Using the PACT Resources Framework, we identified facility‐, clinic‐, and team‐level resources critical for GeriPACT implementation. Resources within each level reflect how the needs of older adults with complex comorbidity intersect with general population primary care medical home practice. GeriPACT implementation is facilitated by attention to patient characteristics such as cognitive impairment, ambulatory limitations, or social support services in staffing and resourcing teams.

CONCLUSION

Models of geriatric primary care such as GeriPACT must be implemented with an eye toward the most effective use of our most limited resource‐trained geriatricians. In contrast to much of the literature on medical home teams serving a general adult population, interviews with GeriPACT members emphasize how patient needs inform all aspects of practice design including universal accessibility, near real‐time response to patient needs, and ongoing interdisciplinary care coordination. Examination of GeriPACT implementation resources through the lens of traditional primary care teams illustrates the importance of tailoring primary care design to the needs of older adults with complex comorbidity.
Comparison between criteria for diagnosing malnutrition in patients with advanced chronic liver disease: GLIM group proposal versus different nutritional screening tools
Authors: Boulhosa R. S. S. B. , Lourenço R. P. , Côrtes D. M. , Oliveira L. P. M. , Lyra A. C. , de Jesus R. P.
Published: May 2020

Background

Different nutritional screening instruments can be used to identify the risk of malnutrition in advanced chronic liver disease patients. The present study aimed to evaluate and compare two nutrition screening tools with the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria for malnutrition in patients with advanced chronic liver disease.

Methods

Two nutritional screening tools, Nutritional Risk Screening 2002 (NRS‐2002) and Royal Free Hospital Nutritional Prioritizing Tool (RFH‐NPT), were assessed for 166 patients with liver cirrhosis. We compared medium/high nutritional risk screening with the diagnosis of malnutrition, using the GLIM criteria as the reference standard.

Results

According to the GLIM criteria, 57.3% of the patients were malnourished. NRS and RFH‐NPT identified, respectively, 36.1% and 52.4% of patients with nutritional risk. RFH‐NPT presented better agreement with the diagnosis according to GLIM criteria (k = 0.64; 95% confidence interval = 0.52–0.75), higher sensitivity (80%), higher negative predictive value (79%) and larger area under the curve (82.3%) compared to the NRS.

Conclusions

RFH‐NPT, when compared with the GLIM method, has substantial agreement in identifying nutritional risk, good sensitivity and good value for diagnosing malnutrition in patients with advanced chronic liver disease.
Canopy composition and drought shape understorey plant assemblages in a young tree diversity experiment
Authors: Corcket Emmanuel , Alard Didier , van Halder Inge , Jactel Hervé , Garrido Diaz Begoña , Reuzeau Edith , Castagneyrol Bastien
Published: May 2020

Questions

Tree diversity is key to the functioning of forest ecosystems. However, which components of tree diversity are responsible for tree diversity effects on associated organisms, and in which context, is poorly understood.

Location

ORPHEE Experimental site, Cestas–Pierroton in the southwest of France.

Methods

We used a large‐scale tree diversity experiment in which we controlled water availability by an irrigation treatment to address tree diversity and water stress effects on the diversity and height of forest understorey vegetation. We assessed the species richness and height of understorey vegetation in irrigated and non‐irrigated 20 m × 20 m plots, either being monocultures of Pinus pinaster, Betula pendula or Quercus robur, or either mixtures of two to five species among Pinus pinaster, Betula pendula, Quercus robur, Quercus ilex and Quercus pyrenaica.

Results

Tree species composition, i.e. the proportion of birch or pine, had a significant effect on understorey plant assemblage, species richness and diversity. The proportion of the fast‐growing deciduous angiosperm Betula pendula was negatively correlated to understorey plant richness and diversity, and positively correlated with understorey vegetation height. Understorey vegetation was higher in irrigated plots than in non‐irrigated plots, but irrigation had no clear effect on the species richness, diversity or composition of understorey plant assemblages.

Conclusions

Forest tree species composition and in particular the relative proportions of different tree species had stronger effects on understorey plants than tree species richness per se. These effects were consistent across irrigation treatments. Even in young forest plantations, effects of tree mixture on understorey vegetation may be observed and seem mainly driven by the functional type of tree in the canopy and initial dynamics of plant regeneration in planted forests.
Comparative efficiency of oestrus synchronization in sheep with progesterone/eCG and progesterone/GnRH during breeding and non‐breeding season
Authors: Santos‐Jimenez Zurisaday , Martinez‐Herrero Claudia , Encinas Teresa , Martinez‐Ros Paula , Gonzalez‐Bulnes Antonio
Published: May 2020

The present study compared the occurrence of oestrus behaviour and ovulation in response to the insertion of CIDR devices plus a classical treatment with equine chorionic gonadotrophin (eCG; single dose at CIDR removal) or alternative treatments with gonadotrophin‐releasing hormone (GnRH, either in a single dose at 56 hr after CIDR removal, or in one dose at CIDR insertion and another dose at 56 hr after CIDR removal). The appearance of oestrus behaviour during reproductive season ranged between 84% and 95% and all females showing oestrus signs had subsequent ovulations. The response, during seasonal anoestrus, was similar in the group treated with eCG, but less than half of the females in the groups treated with GnRH showed oestrus signs in response to the treatment, although more than 80% of them showed resumption of ovulatory activity after the treatment. In conclusion, protocols based on GnRH administration offer similar yields to eCG‐based protocols during the reproductive season but occurrence of oestrus in response to GnRH‐based treatments is highly compromised during seasonal anoestrus.
Factors associated with quality of life for children affected by parental illness or substance abuse
Authors: Kallander Ellen Katrine , Weimand Bente M. , Hanssen‐Bauer Ketil , Van Roy Betty , Ruud Torleif
Published: May 2020

Background

There have been inconsistent findings from studies examining factors associated with quality of life (QoL) for children affected by parental illness.

Aim

The aim of this study was to explore factors associated with self‐reported QoL in children affected by parental illness or parental substance abuse.

Design

A cross‐sectional multicentre study.

Methods

The sample included 246 families with children 8–18 years recruited via ill parents who received treatment for severe physical illness, mental illness or substance abuse in specialised health services. We performed multiple linear regression analyses to examine factors associated with the children’s self‐reported QoL.

Main outcome measure

KIDSCREEN‐27.

Results

The children’s self‐reported QoL was positively associated with the ill parent’s self‐reported physical health, the children’s self‐reported social skills, the degree to which other adults took over the ill parent’s responsibilities, provision of sibling care, provision of health care for the ill parent and positive outcome of caregiving. The children’s QoL was negatively associated with the children’s self‐reported responsibilities due to parental illness, provision of emotional care for the ill parent, negative outcomes of caregiving and external locus of control. The model explained 63% of the variance (adjusted R2) in children’s total QoL.

Study limitations

Sampling bias may have occurred during recruitment.

Conclusions

The findings suggest factors of importance for the children’s QoL. Clinicians should assess whether an ill parent’s physical health may influence negatively on their ability to perform daily responsibilities at home and care for their children, and clinicians can use children’s self‐reported QoL to identify children who are most negatively affected.
The Effects of the Short Foot Exercise on Navicular Drop: A Critically Appraised Topic
Authors: Haun Cameron , Brown Cathleen N. , Hannigan Kimberly , Johnson Samuel T.
Published: May 2020

Clinical Scenario: Deformation of the arch, as measured by navicular drop (ND), is linked to lower-extremity musculoskeletal injuries. The short foot exercise (SFE) has been used to strengthen the intrinsic foot muscles that support the arch. Clinical Question: Does the SFE decrease ND in healthy adults? Summary of Key Findings: Three studies that examined the use of the SFE on ND were included. A randomized control trial that compared the SFE to a towel-curl exercise and a control group found no significant differences between the 3 groups. A randomized control trial compared the SFE to the use of arch support insoles in individuals with a flexible flatfoot and found a significant improvement in the SFE group. A prospective cohort study, without a control group, reported a significant decrease in ND following a 4-week SFE intervention without a regression at an 8-week follow-up. Overall, two of the three studies reported a significant reduction in ND following an SFE. Clinical Bottom Line: There is preliminary data supporting the use of the SFE to decrease ND—particularly in individuals with a flexible flatfoot. However, issues with the study designs make it difficult to interpret the data. Strength of Recommendation: Due to limited evidence, there is grade B evidence to support the use of the SFE to decrease ND.
Comparison of Two High-Throughput Reverse Transcription-PCR Systems for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Craney Arryn R. , Velu Priya D. , Satlin Michael J. , Fauntleroy Kathy A. , Callan Katrina , Robertson Amy , La Spina Marisa , Lei Beryl , Chen Anqi , Alston Tricia , Rozman Anna , Loda Massimo , Rennert Hanna , Cushing Melissa , Westblade Lars F.
Published: May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the cause of a worldwide pandemic. Many commercial SARS-CoV-2 reverse transcription-PCR (RT-PCR) assays have received Emergency Use Authorization from the U.S. Food and Drug Administration. However, there are limited data describing their performance, in particular the performance of high-throughput SARS-CoV-2 RT-PCR systems. We analyzed the diagnostic performance of two high-throughput systems: cobas 6800 and Panther Fusion, and their associated RT-PCR assays, with a collection of 389 nasopharyngeal specimens.
Supplemental Material: Loess in eastern equatorial Pangea archives a dusty atmosphere and possible upland glaciation
Authors: Pfeifer Lily S.
Published: May 2020

Sample location table (locations of measured sections and GPS coordinates of all samples collected for grain size, geochronological, and geochemical analysis) as well as supplementary images that were acquired for grain size analysis ("Appendix I").
Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study
Authors: Richardson Tom G , Sanderson Eleanor , Elsworth Benjamin , Tilling Kate , Davey Smith George
Published: May 2020

Objective

To evaluate whether body size in early life has an independent effect on risk of disease in later life or whether its influence is mediated by body size in adulthood.

Design

Two sample univariable and multivariable mendelian randomisation.

Setting

The UK Biobank prospective cohort study and four large scale genome-wide association studies (GWAS) consortiums.

Participants

453 169 participants enrolled in UK Biobank and a combined total of more than 700 000 people from different GWAS consortiums.

Exposures

Measured body mass index during adulthood (mean age 56.5) and self-reported perceived body size at age 10.

Main outcome measures

Coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer.

Results

Having a larger genetically predicted body size in early life was associated with an increased odds of coronary artery disease (odds ratio 1.49 for each change in body size category unless stated otherwise, 95% confidence interval 1.33 to 1.68) and type 2 diabetes (2.32, 1.76 to 3.05) based on univariable mendelian randomisation analyses. However, little evidence was found of a direct effect (ie, not through adult body size) based on multivariable mendelian randomisation estimates (coronary artery disease: 1.02, 0.86 to 1.22; type 2 diabetes:1.16, 0.74 to 1.82). In the multivariable mendelian randomisation analysis of breast cancer risk, strong evidence was found of a protective direct effect for larger body size in early life (0.59, 0.50 to 0.71), with less evidence of a direct effect of adult body size on this outcome (1.08, 0.93 to 1.27). Including age at menarche as an additional exposure provided weak evidence of a total causal effect (univariable mendelian randomisation odds ratio 0.98, 95% confidence interval 0.91 to 1.06) but strong evidence of a direct causal effect, independent of early life and adult body size (multivariable mendelian randomisation odds ratio 0.90, 0.85 to 0.95). No strong evidence was found of a causal effect of either early or later life measures on prostate cancer (early life body size odds ratio 1.06, 95% confidence interval 0.81 to 1.40; adult body size 0.87, 0.70 to 1.08).

Conclusions

The findings suggest that the positive association between body size in childhood and risk of coronary artery disease and type 2 diabetes in adulthood can be attributed to individuals remaining large into later life. However, having a smaller body size during childhood might increase the risk of breast cancer regardless of body size in adulthood, with timing of puberty also putatively playing a role.
Accelerated, Dose escalated, Sequential Chemoradiotherapy in Non-small-cell lung cancer (ADSCaN): a protocol for a randomised phase II study
Authors: Hatton Matthew Q F , Lawless Claire Anne , Faivre-Finn Corinne , Landau David , Lester Jason F , Fenwick John , Simões Rita , McCartney Elaine , Boyd Kathleen Anne , Haswell Tom , Shaw Ann , Paul James
Published: May 2020

Introduction

Lung cancer is the most common cause of cancer mortality in the UK, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients present with inoperable disease; therefore, radiotherapy plays a major role in treatment. However, the majority of patients are not suitable for the gold standard treatment (concurrent chemoradiotherapy) due to performance status and comorbidities. Novel strategies integrating radiotherapy advances and radiobiological knowledge need to be evaluated in patients treated with sequential chemoradiotherapy. Four separate dose escalation accelerated radiotherapy schedules have been completed in UK (CHART-ED, IDEAL-CRT, I-START and Isotoxic IMRT). This study will compare these schedules with a UK standard sequential chemoradiotherapy schedule of 55 Gy in 20 fractions over 4 weeks. As it would be impossible to test all schedules in a phase III study, the aim is to use a combined randomised phase II screening/‘pick the winner’ approach to identify the best schedule to take into a randomised phase III study against conventionally fractionated radiotherapy.

Methods and analysis

Suitable patients will have histologically/cytologically confirmed, stage III NSCLC and are able to undergo chemoradiotherapy treatment. The study will recruit 360 patients; 120 on the standard arm and 60 on each experimental arm. Patients will complete 2–4 cycles of platinum-based chemotherapy before being randomised to one of the radiotherapy schedules. The primary endpoint is progression-free survival, with overall survival, time to local–regional failure, toxicity and cost-effectiveness as secondary objectives.

Ethics and dissemination

The study has received ethical approval (research ethics committee (REC) reference: 16/WS/0165) from the West of Scotland REC 1. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Trial results will be published in a peer-reviewed journal and presented internationally.

Trial registration number

ISRCTN47674500.
Robot-assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy (iROC): protocol for a randomised controlled trial with internal feasibility study
Authors: Catto James W F , Khetrapal Pramit , Ambler Gareth , Sarpong Rachael , Khan Muhammad Shamim , Tan Melanie , Feber Andrew , Dixon Simon , Goodwin Louise , Williams Norman R , McGrath John , Rowe Edward , Koupparis Anthony , Brew-Graves Chris , Kelly John D
Published: May 2020

Introduction

Bladder cancer (BC) is a common malignancy and one of the most expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a gold standard treatment for high-risk BC. Reductions in morbidity and mortality from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons between open RC (ORC) and RARC have been limited by sample size, use of extracorporeal reconstruction and use of outcomes important for ORC. Conversely, while RARC is gaining in popularity, there is little evidence to suggest it is superior to ORC. We are undertaking a prospective randomised controlled trial (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using multimodal outcomes to explore qualitative and quantitative recovery after surgery.

Methods and analysis

iROC is a multicentre prospective RCT in English National Health Service (NHS) cancer centres. We will randomise 320 patients undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial entry and consent. The primary outcome is days alive and out of hospital within the first 90 days from surgery. Secondary outcomes will measure functional recovery (activity trackers, chair-to-stand tests and health related quality of life (HRQOL) questionnaires), morbidity (complications and readmissions), cost-effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and surgeon fatigue. Patients will be analysed according to intention to treat. The primary outcome will be transformed and analysed using regression. All statistical assumptions will be investigated. Secondary outcomes will be analysed using appropriate regression methods. An internal feasibility study of the first 30 patients will evaluate recruitment rates, acceptance of randomised treatment choice, compliance outcome collection and to revise our sample size.

Ethics and dissemination

The study has ethical approval (REC reference 16/NE/0418). Findings will be made available to patients, clinicians, funders and the NHS through peer-reviewed publications, social media and patient support groups.

Trial registration numbers

ISRCTN13680280andNCT03049410.
Cognitive-behavioural therapy (CBT) for renal fatigue (BReF): a feasibility randomised-controlled trial of CBT for the management of fatigue in haemodialysis (HD) patients
Authors: Picariello Federica , Moss-Morris Rona , Macdougall Iain C , Norton Sam , Da Silva-Gane Maria , Farrington Ken , Clayton Hope , Chilcot Joseph
Published: May 2020

Introduction

Fatigue is one of the most common and disabling symptoms in end-stage kidney disease, particularly among in-centre haemodialysis patients. This two-arm parallel group feasibility randomised controlled trial will determine whether a fully powered efficacy trial is achievable by examining the feasibility of recruitment, acceptability and potential benefits of a cognitive-behavioural therapy (CBT)-based intervention for fatigue among in-centre haemodialysis patients.

Methods

We aim to recruit 40 adult patients undergoing in-centre haemodialysis at secondary care outpatient dialysis units, who meet clinical levels of fatigue. Patients will be randomised individually (using a 1:1 ratio) to either a 4–6 weeks’ CBT-based intervention (intervention arm) or to a waiting-list control (control arm). The primary feasibility outcomes include descriptive data on numbers within each recruiting centre meeting eligibility criteria, rates of recruitment, numbers retained postrandomisation and treatment adherence. To assess the potential benefits of the cognitive-behavioural therapy for renal fatigue intervention, secondary self-report outcomes include measures of fatigue severity (Chalder Fatigue Questionnaire), fatigue-related functional impairment (Work and Social Adjustment Scale), sleep quality (Pittsburgh Sleep Quality Index), depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). Changes in fatigue perceptions (Brief Illness Perception Questionnaire), cognitive and behavioural responses to fatigue (Cognitive and Behavioural Responses to Symptoms Questionnaire), sleep hygiene behaviours (Sleep Hygiene Index) and physical activity (International Physical Activity Questionnaire–short form) will also be explored. These self-report measures will be collected at baseline and 3 months postrandomisation. Nested qualitative interviews will be conducted postintervention to explore the acceptability of the intervention and identify any areas in need of improvement. The statistician and assessor will be blinded to treatment allocation.

Ethics and dissemination

A National Health Service (NHS) Research Ethics Committee approved the study. Any amendments to the protocol will be submitted to the NHS Committee and study sponsor.

Trial registration number

ISRCTN91238019;Pre-results.
Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study
Authors: Liu Hanning , Xu Zhengxi , Sun Cheng , Chen Qianlong , Bao Ning , Chen Wen , Zhou Zhou , Wang Xiaoqi , Zheng Zhe
Published: May 2020

Objective

As a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is associated with major adverse cardiac and cerebrovascular events (MACCE) after coronary artery bypass graft (CABG) surgery, we designed a nested case-control study.

Design

Observational, nested case-control study.

Setting

Single-centre outcomes research in Fuwai Hospital, Beijing, China.

Participants

One thousand six hundred and seventy Chinese patients undergoing CABG surgery from September 2011 to October 2013.

Methods

We obtained urinary samples from 1670 Chinese patients undergoing CABG 1 hour before surgery (pre-CABG), and 6 hours (post-CABG 6 hours) and 24 hours after surgery (post-CABG 24 hours). Patients were followed up for 1 year, and we observed 56 patients had MACCE. For each patient with MACCE, we matched three control subjects. Perioperative urinary TXA-M of the three time spots was detected in these 224 patients.

Results

Post-CABG 24 hours TXA-M is significantly higher than that of patients without MACCE (11 101vs8849 pg/mg creatine, P=0.007). In addition, patients in the intermediate tertile and upper tertile of post-CABG 24 hours urinary TXA-M have a 2.2 times higher (HR 2.22, 95% CI 1.04 to 4.71, P=0.038) and a 2.8 times higher (HR 2.81, 95% CI 1.35 to 5.85, P=0.006) risk of 1 year MACCE than those in the lower tertile, respectively.

Conclusions

In conclusion, post-CABG 24 hours urinary TXA-M elevation is associated with an increase of 1 year adverse events after CABG, indicating that the induction of cyclo-oxygenase-2 by surgery-related inflammatory stimuli or platelet turnover may be responsible for the high levels of post-CABG urinary TXA-M.

Trial registration number

NCT01573143.
Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study
Authors: Jitsumura Maki , Cunningham Andrew Laurence , Hitchings Matthew David , Islam Saiful , Davies Angharad P , Row Paula E , Riddell Andrew D , Kinross James , Wilkinson Tom S , Jenkins G J , Williams John G , Harris Dean Anthony
Published: May 2020

Background

The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response.

Methods and analysis

This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40 cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study.

Ethics and dissemination

The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University’s Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared with trial participants.

Trial registration number

ISRCTN58082603; Pre-results.
Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I/II clinical trial
Authors: Zhao Tian Xiao , Kostapanos Michalis , Griffiths Charmaine , Arbon Emma L , Hubsch Annette , Kaloyirou Fotini , Helmy Joanna , Hoole Stephen P , Rudd James H F , Wood Graham , Burling Keith , Bond Simon , Cheriyan Joseph , Mallat Ziad
Published: May 2020

Introduction

Inflammation and dysregulated immune responses play a crucial role in atherosclerosis, underlying ischaemic heart disease (IHD) and acute coronary syndromes (ACSs). Immune responses are also major determinants of the postischaemic injury in myocardial infarction. Regulatory T cells (CD4+CD25+FOXP3+; Treg) induce immune tolerance and preserve immune homeostasis. Recent in vivo studies suggested that low-dose interleukin-2 (IL-2) can increase Treg cell numbers. Aldesleukin is a human recombinant form of IL-2 that has been used therapeutically in several autoimmune diseases. However, its safety and efficacy is unknown in the setting of coronary artery disease.

Method and analysis

Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes is a single-centre, first-in-class, dose-escalation, two-part clinical trial. Patients with stable IHD (part A) and ACS (part B) will be randomised to receive either IL-2 (aldesleukin; dose range 0.3–3×106IU) or placebo once daily, given subcutaneously, for five consecutive days. Part A will have five dose levels with five patients in each group. Group 1 will receive a dose of 0.3×106IU, while the dose for the remaining four groups will be determined on completion of the preceding group. Part B will have four dose levels with eight patients in each group. The dose of the first group will be based on part A. Doses for each of the subsequent three groups will similarly be determined after completion of the previous group. The primary endpoint is safety and tolerability of aldesleukin and to determine the dose that increases mean circulating Treg levels by at least 75%.

Ethics and dissemination

The study received a favourable opinion by the Greater Manchester Central Research Ethics Committee, UK (17/NW/0012). The results of this study will be reported through peer-reviewed journals, conference presentations and an internal organisational report.

Trial registration number

NCT03113773; Pre-results.
Proinsulin in the identification and risk stratification of gestational diabetes mellitus: study protocol for a prospective, longitudinal cohort study
Authors: Peter Rajesh , Bright Dominic , Cheung Wai-Yee , Luzio Stephen D , Dunseath Gareth J
Published: May 2020

Introduction

Gestational diabetes mellitus (GDM) is a common metabolic disorder occurring in up to 10% of pregnancies in the western world. Most women with GDM are asymptomatic; therefore, it is important to screen, diagnose and manage the condition as it is associated with an increased risk of maternal and perinatal complications. Diagnosis of GDM is made in the late second trimester or early third trimester because accurate diagnosis or risk stratification in the first trimester is still lacking. An increase in serum proinsulin may be seen earlier in pregnancy and before a change in glycaemic control can be identified. This study will aim to establish if fasting proinsulin concentrations at 16–18 weeks gestation will help to identify or risk stratify high-risk pregnant women with GDM.

Methods and analysis

This is a prospective, longitudinal cohort study. Two oral glucose tolerance tests will be carried out at 16–18 and 24–28 weeks gestation in 200 pregnant women with at least one risk factor for GDM (body mass index>30 kg/m2, previous macrosomic baby (>4.5 kg), previous gestational diabetes, first degree relative with type 2 diabetes mellitus) recruited from antenatal clinics. Blood samples will be taken fasting and at 30 min, 1 and 2 hours following the 75 g glucose load. In addition, a fasting blood sample will be taken 6-weeks post delivery. All samples will be analysed for glucose, insulin, C peptide and proinsulin. Recruitment began in November 2017. Optimal cut-off points for proinsulin to diagnose gestational diabetes according to National Institute for Health and Care Excellence (2015) criteria will be established by the receiver operating characteristic plot and sensitivity and specificity will be calculated to assess the diagnostic accuracy of proinsulin at 16–18 weeks gestation.

Ethics and dissemination

This study received ethical approval from the Wales Research Ethics Committee (Panel 6) (Ref. 17/WA/0194). Data will be presented at international conferences and published in peer-reviewed journals.

Trial registration number

ISRCTN16416602; Pre-results.
Efficacy of a standardised acupuncture approach for women with bothersome menopausal symptoms: a pragmatic randomised study in primary care (the ACOM study)
Authors: Lund Kamma Sundgaard , Siersma Volkert , Brodersen John , Waldorff Frans Boch
Published: May 2020

Objective

To investigate the efficacy of a standardised brief acupuncture approach for women with moderate-to-severe menopausal symptoms.

Design

Randomised and controlled, with 1:1 allocation to the intervention group or the control group. The assessor and the statistician were blinded.

Setting

Nine Danish primary care practices.

Participants

70 women with moderate-to-severe menopausal symptoms and nine general practitioners with accredited education in acupuncture.

Intervention

The acupuncture style was western medical with a standardised approach in the predefined acupuncture points CV-3, CV-4, LR-8, SP-6 and SP-9. The intervention group received one treatment for five consecutive weeks. The control group was offered treatment after 6 weeks.

Main outcome measures

Outcomes were the differences between the randomisation groups in changes to mean scores using the scales in the MenoScores Questionnaire, measured from baseline to week 6. The primary outcome was the hot flushes scale; the secondary outcomes were the other scales in the questionnaire. All analyses were based on intention-to-treat analysis.

Results

36 participants received the intervention, and 34 participants were in the control group. Four participants dropped out before week 6. The acupuncture intervention significantly decreased hot flushes: Δ −1.6 (95% CI [−2.3 to −0.8]; p<0.0001), day-and-night sweats: Δ −1.2 (95% CI [−2.0 to −0.4]; p=0.0056), general sweating: Δ −0.9(95% CI [−1.6 to −0.2]; p=0.0086), menopausal-specific sleeping problems: Δ −1.8 (95% CI [−2.7 to −1.0]; p<0.0001), emotional symptoms: Δ −3.4 (95% CI [−5.3 to −1.4]; p=0.0008), physical symptoms: Δ −1.7 (95% CI [−3 to −0.4]; p=0.010) and skin and hair symptoms: Δ −1.5 (95% CI [−2.5 to −0.6]; p=0.0021) compared with the control group at the 6-week follow-up. The pattern of decrease in hot flushes, emotional symptoms, skin and hair symptoms was already apparent 3 weeks into the study. Mild potential adverse effects were reported by four participants, but no severe adverse effects were reported.

Conclusions

The standardised and brief acupuncture treatment produced a fast and clinically relevant reduction in moderate-to-severe menopausal symptoms during the six-week intervention. No severe adverse effects were reported.

Trial registration number

NCT02746497; Results.
ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for an interventional randomised controlled trial
Authors: China Louise , Skene Simon S , Bennett Kate , Shabir Zainib , Hamilton Roseanna , Bevan Scott , Chandler Torsten , Maini Alexander A , Becares Natalia , Gilroy Derek , Forrest Ewan H , O’Brien Alastair
Published: May 2020

Introduction

Circulating prostaglandin E2levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds to and inactivates this immune-suppressive lipid mediator. Human albumin solution (HAS) could thus be repurposed as an immune-restorative drug in these patients.

This is a phase III randomised controlled trial (RCT) to verify whether targeting a serum albumin level of ≥35 g/L in hospitalised patients with decompensated cirrhosis using repeated intravenous infusions of 20% HAS will reduce incidence of infection, renal dysfunction and mortality for the treatment period (maximum 14 days or discharge if <14 days) compared with standard medical care.

Methods and analysis

Albumin To prevenT Infection in chronic liveR failurE stage 2 is a multicentre, open-label, interventional RCT. Patients with decompensated cirrhosis admitted to the hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Patients randomised to intravenous HAS will have this administered, according to serum albumin levels, for up to 14 days or discharge. The infusion protocol aims to increase serum albumin to near-normal levels.

The composite primary endpoint is: new infection, renal dysfunction or mortality within the trial treatment period. Secondary endpoints include mortality at up to 6 months, incidence of other organ failures, cost-effectiveness and quality of life outcomes and time to liver transplant. The trial will recruit 866 patients at more than 30 sites across the UK.

Ethicsanddissemination

Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001–0001). The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the National Institute for Health Research (ISRCTN14174793). This manuscript refers to version 6.0 of the protocol. Results will be disseminated through peer-reviewed journals and international conferences. Recruitment of the first participant occurred on 25 January 2016.
General practitioners and emergency departments (GPED)—efficient models of care: a mixed-methods study protocol
Authors: Morton Katherine , Voss Sarah , Adamson Joy , Baxter Helen , Bloor Karen , Brandling Janet , Cowlishaw Sean , Doran Tim , Gibson Andrew , Gutacker Nils , Liu Dan , Purdy Sarah , Roy Paul , Salisbury Christopher , Scantlebury Arabella , Vaittinen Anu , Watson Rose , Benger Jonathan Richard
Published: May 2020

Introduction

Pressure continues to grow on emergency departments in the UK and throughout the world, with declining performance and adverse effects on patient outcome, safety and experience. One proposed solution is to locate general practitioners to work in or alongside the emergency department (GPED). Several GPED models have been introduced, however, evidence of effectiveness is weak. This study aims to evaluate the impact of GPED on patient care, the primary care and acute hospital team and the wider urgent care system.

Methods and analysis

The study will be divided into three work packages (WPs). WP-A; Mapping and Taxonomy: mapping, description and classification of current models of GPED in all emergency departments in England and interviews with key informants to examine the hypotheses that underpin GPED. WP-B; Quantitative Analysis of National Data: measurement of the effectiveness, costs and consequences of the GPED models identified in WP-A, compared with a no-GPED model, using retrospective analysis of Hospital Episode Statistics Data. WP-C; Case Studies: detailed case studies of different GPED models using a mixture of qualitative and quantitative methods including: non-participant observation of clinical care, semistructured interviews with staff, patients and carers; workforce surveys with emergency department staff and analysis of available local routinely collected hospital data. Prospective case study sites will be identified by completing telephone interviews with sites awarded capital funding by the UK government to implement GPED initiatives. The study has a strong patient and public involvement group that has contributed to study design and materials, and which will be closely involved in data interpretation and dissemination.

Ethics and dissemination

The study has been approved by the National Health Service East Midlands—Leicester South Research Ethics Committee: 17/EM/0312. The results of the study will be disseminated through peer-reviewed journals, conferences and a planned programme of knowledge mobilisation.

Trial registration number

ISRCTN51780222.
The HARMONIC trial: study protocol for a randomised controlled feasibility trial of Shaping Healthy Minds—a modular transdiagnostic intervention for mood, stressor-related and anxiety disorders in adults
Authors: Black Melissa , Hitchcock Caitlin , Bevan Anna , O Leary Cliodhna , Clarke James , Elliott Rachel , Watson Peter , LaFortune Louise , Rae Sarah , Gilbody Simon , Kuyken Willem , Johnston David , Newby Jill M , Dalgleish Tim
Published: May 2020

Introduction

Anxiety, mood and trauma-related disorders are common, affecting up to 20% of adults. Many of these individuals will experience symptoms of more than one disorder as diagnostically defined. However, most psychological treatments focus on individual disorders and are less effective for those who experience comorbid disorders. The Healthy and Resilient Mind Programme: Building Blocks for Mental Wellbeing (HARMONIC) trial introduces a novel transdiagnostic intervention (Shaping Healthy Minds (SHM)), which synthesises several evidence-based treatment techniques to address the gap in effective interventions for people with complex and comorbid difficulties. This early phase trial aims to estimate the efficacy and feasibility of the transdiagnostic intervention in preparation for a later-phase randomised controlled trial, and to explore mechanisms of change.

Methods/analysis

We outline a patient-level two-arm randomised controlled trial (HARMONIC) that comparesSHMto treatment-as-usual for individuals aged >18 years (n=50) with comorbid mood, anxiety, obsessive-compulsive or trauma/stressor disorders diagnoses, recruited from outpatient psychological services within the UK National Health Service (NHS). The co-primary outcomes will be 3-month follow-up scores on self-report measures of depressive symptoms, anxiety symptoms, and disability and functional impairment. Secondary outcomes include changes in symptoms linked to individual disorders. We will assess the feasibility and acceptability ofSHM, the utility of proposed outcome measures, and refine the treatment manuals in preparation for a later-phase trial.

Ethics and dissemination

This trial protocol has been approved by the Health Research Authority of the NHS of the UK (East of England, Reference: 16/EE/0095). We anticipate that trial findings will inform future revisions of clinical guidelines for numerous forms of mood, anxiety and stressor-related disorders. Findings will be disseminated broadly via peer-reviewed empirical journal articles, conference presentations, clinical workshops and a trial website.

Trial registration

NCT03143634; Pre-results.
Barriers to accessing mental health services for women with perinatal mental illness: systematic review and meta-synthesis of qualitative studies in the UK
Authors: Sambrook Smith Megan , Lawrence Vanessa , Sadler Euan , Easter Abigail
Published: May 2020

Objective

Lack of access to mental health services during the perinatal period is a significant public health concern in the UK. Barriers to accessing services may occur at multiple points in the care pathway. However, no previous reviews have investigated multilevel system barriers or how they might interact to prevent women from accessing services. This review examines women, their family members’ and healthcare providers’ perspectives of barriers to accessing mental health services for women with perinatal mental illness in the UK.

Design

A systematic review and meta-synthesis of qualitative studies.

Data sources

Qualitative studies, published between January 2007 and September 2018, were identified in MEDLINE, PsycINFO, EMBASE and CINAHL electronic databases, handsearching of reference lists and citation tracking of included studies. Papers eligible for inclusion were conducted in the UK, used qualitative methods and were focused on women, family or healthcare providers working with/or at risk of perinatal mental health conditions. Quality assessment was conducted using the Critical Appraisal Skills Programme for qualitative studies.

Results

Of 9882 papers identified, 35 studies met the inclusion criteria. Reporting of emergent themes was informed by an existing multilevel conceptual model. Barriers to accessing mental health services for women with perinatal mental illness were identified at four levels: Individual (eg, stigma, poor awareness), organisational (eg, resource inadequacies, service fragmentation), sociocultural (eg, language/cultural barriers) and structural (eg, unclear policy) levels.

Conclusions

Complex, interlinking, multilevel barriers to accessing mental health services for women with perinatal mental illness exist. To improve access to mental healthcare for women with perinatal mental illness multilevel strategies are recommended which address individual, organisational, sociocultural and structural-level barriers at different stages of the care pathway.

PROSPERO registration number

CRD42017060389.
Effects of vestibular rehabilitation, with or without betahistine, on managing residual dizziness after successful repositioning manoeuvres in patients with benign paroxysmal positional vertigo: a protocol for a randomised controlled trial
Authors: Wu Peixia , Cao Wenzhu , Hu Yan , Li Huawei
Published: May 2020

Introduction

Benign paroxysmal positional vertigo (BPPV) is recognised as the leading cause of peripheral vertigo in adults. The canalith repositioning procedure (CRP) can be used for effective treatment of BPPV. However, some patients experience residual dizziness (RD) even after successful CRP, resulting in a significant negative impact on their daily function and quality of life. Exercise-based vestibular rehabilitation (VR) has been proven as an effective method for managing dizziness and has been applied in patients with various vestibular disorders. However, the efficacy of VR to specifically target RD post-BPPV is unknown. This study aims to investigate the efficacy of VR, compared with betahistine or VR plus betahistine treatment, in the treatment of patients experiencing RD after successful CRP.

Methods and analysis

A randomised single-blinded controlled trial will be carried out to determine the efficacy of VR compared with betahistine or VR plus betahistine treatment in mitigating RD and improving balance function. Patients with BPPV who experience RD after successful CRP will be recruited. Participants will be randomised into one of three groups to receive VR, betahistine or VR plus betahistine. There will be 61 participants in each group. The primary outcomes will be changes in the patient’s daily function as measured by the Vestibular Activities and Participation questionnaire and balance ability assessed by computerised dynamic posturography. The secondary outcomes will be dizziness-related handicap, otolith function and duration of RD symptoms. Outcome measures will be noted at baseline and at 2, 4 and 8 weeks post-randomisation. This study has the potential to reduce unnecessary anti-vertigo drug prescriptions and may lead to a general consensus regarding the use of VR as a first-line treatment for RD in patients with BPPV.

Ethics and dissemination

This trial received ethical approval from the Institutional Review Board of Eye and ENT Hospital of Fudan University (reference number 2017046). The study results will be disseminated via peer-reviewed journals and conferences.

Trial registration number

NCT03624283; Pre-results.