bluuebunny/crossref_metadata_2025 huggingface dataset:
Resilience of Metrorail Networks: Quantification With Washington, DC as a Case Study
Authors: Saadat Yalda , Ayyub Bilal M. , Zhang Yanjie , Zhang Dongming , Huang Hongwei
Published: June 2019

According to the United Nation's Department of Economic and Social Affairs Population Division, 66% of the world's population will reside in urban areas by 2050, a boost from 30% in 1950. Urbanization has indeed triumphed and has increased the demand for infrastructure systems including metrorail networks, one of the most tangible examples of complex transportation infrastructure systems. A synergistic rapid growth of urban population concurrent with great increases in metrorail use may lead to perturbations in the state of such a system. Taking into consideration of such perturbations and developing appropriate resilience measurements are paramount to the design of sustainable, robust, and resilient systems capable of performing satisfactorily through intentional and/or stochastic disruptions. As such, developing resilience metrics in a structured and appropriate manner is necessary. Using Washington, DC Metro as a case study, this paper examines metrorail network resilience and associated metrics with well-defined relationships to vulnerability and tied to efficiency. This examination includes developing a metro rail model in a graph form and obtaining its basic features by network topology analysis. The analytical work demonstrates that the Washington, DC Metro with its 91 stations and 140 links is a small-world network with the presence of a scale-free phenomenon and of a high level of vulnerability in the case of disruptive events. Evaluation of the efficiency and vulnerability of a metrorail network after disruption requires the consideration of two primary failure events, i.e., the failure of a metro station and the failure of a metro segment between stations. Vulnerability evaluation identifies the most critical stations and rail segments as illustrated using the Washington, DC Metro network. Such an assessment offers a logical basis to enhance system resilience and develop postfailure recovery strategies.
Evaluation of Parametric Models Dedicated to a Magnetorheological Actuator Including Uncertainty and Sensitivity Analyses
Authors: Teixeira Philippe C. Fernandes , Saad Núbia dos Santos , Lara-Molina Fabian Andres , Cavalini Aldemir Ap , Steffen Valder
Published: June 2019

Semi-active actuators have been used in engineering systems for vibration control purposes. For instance, magnetorheological (MR) dampers are applied in support of vehicle seats and smart suspensions of bridges and buildings. Parametric and nonparametric approaches were developed to model MR actuators, in which the former presents well-established and representative models. In this context, this work aims at comparing the so-called Bingham, modified Bouc-Wen (BW), and hysteretic models dedicated to MR actuators. Typical inverse problems were solved to minimize the difference between the forces determined by using these models and experimental data. The obtained results demonstrated that the hysteretic model is better adapted to represent the considered MR actuator, presenting lower computational cost and easy implementation. Additionally, uncertainty and sensitivity analyses based on the interval approach were applied on the updated MR models aiming to determine the working envelopes associated with the most important parameters of the models.
Structural Reliability Analysis Using Adaptive Artificial Neural Networks
Authors: de Santana Gomes Wellison José
Published: June 2019

Structural reliability theory has been applied to many engineering problems in the last decades, with the primary objective of quantifying the safety of such structures. Although in some cases approximated methods may be used, many times the only alternatives are those involving more demanding approaches, such as Monte Carlo simulation (MCS). In this context, surrogate models have been widely employed as an attempt to keep the computational effort acceptable. In this paper, an adaptive approach for reliability analysis using surrogate models, proposed in the literature in the context of Kriging and polynomial chaos expansions (PCEs), is adapted for the case of multilayer perceptron (MLP) artificial neural networks (ANNs). The methodology is employed in the solution of three benchmark reliability problems and compared to MCS and other methods from the literature. In all cases, the ANNs led to results very close to those obtained by MCS and required much less limit state function evaluations. Also, the performance of the ANNs was found comparable, in terms of accuracy and efficiency, to the performance of the other methods.
Comparing Principal Component Analysis and Mahalanobis–Taguchi System to Detect Unbalance in a Centrifugal Compressor in a Floating Production Storage and Offloading
Authors: de Carvalho Michalski Miguel Angelo , de Melo Italo Skovroski , de Souza Gilberto Francisco Martha
Published: June 2019

Centrifugal compressors used in floating production storage and offloading (FPSO) have special characteristics, forcing manufacturers to build machines that operate at higher speeds in order to achieve the required process performance. Under these operating and design conditions, a special balance procedure called high-speed balancing may be necessary. This procedure is generally done in a special workbench of specialized companies and carrying out a field balance of these machines is an unlikely alternative. Therefore, the development of techniques to identify unbalance malfunction prior to reaching the machine vibration trip limits is essential to minimize the unit downtime. Data-based techniques are strong candidates for the task, since they can take full advantage of huge amounts of available data, allowing the information to be used in an effective way. In this work, two different techniques were chosen to improve unbalance identification: Mahalanobis–Taguchi system (MTS) and principal component analysis (PCA). Considering a real machine, several unbalance conditions were simulated and the results are presented and discussed. Both methods were able to detect unbalance, with a slightly advantage for PCA for the considered conditions.
Dynamic Risk Analysis Using Imprecise and Incomplete Information
Authors: Kamil Mohammad Zaid , Khan Faisal , Song Guozheng , Ahmed Salim
Published: June 2019

Accident modeling is a vital step, which helps in designing preventive measures to avoid future accidents, and thus, to enhance process safety. Bayesian networks (BN) are widely used in accident modeling due to its capability to represent accident scenarios from their causes to likely consequences. However, to assess likelihood of an accident using the BN, it requires exact basic event probabilities, which are often obtained from expert opinions. Such subjective opinions are often inconsistent and sometimes conflicting and/or incomplete. In this work, evidence theory has been coupled with BN to address inconsistency, conflict and incompleteness in the expert opinions. It combines the acquired knowledge from various subjective sources, thereby rendering accuracy in probability estimation. Another source of uncertainty in BN is model uncertainty. To represent multiple interactions of a cause–effect relationship Noisy-OR and leaky Noisy-AND gates are explored in the study. Conventional logic gates, i.e., OR/AND gates can only provide a linear interaction of cause–effect relationship hence introduces uncertainty in the assessment. The proposed methodology provides an impression how dynamic risk assessment could be conducted when the sufficient information about a process system is unavailable. To illustrate the execution of a proposed methodology, a tank equipped with a basic process control system has been used as an example. A real-life case study has also been used to validate the proposed model and compare its results with those using a deterministic approach.
Maximizing Flexibility for Complex Systems Design to Compensate Lack-of-Knowledge Uncertainty
Authors: Daub Marco , Duddeck Fabian
Published: June 2019

The consideration of uncertainty is especially important for the design of complex systems. Because of high complexity, the total system is normally divided into subsystems, which are treated in a hierarchical and ideally independent manner. In recent publications, e.g., (Zimmermann, M., and von Hoessle, J. E., 2013, “Computing Solution Spaces for Robust Design,” Int. J. Numer. Methods Eng., 94(3), pp. 290–307; Fender, J., Duddeck, F., and Zimmermann, M., 2017, “Direct Computation of Solution Spaces,” Struct. Multidiscip. Optim., 55(5), pp. 1787–1796), a decoupling strategy is realized via first the identification of the complete solution space (solutions not violating any design constraints) and second via derivation of a subset, a so-called box-shaped solution space, which allows for decoupling and therefore independent development of subsystems. By analyzing types of uncertainties occurring in early design stages, it becomes clear that especially lack-of-knowledge uncertainty dominates. Often, there is missing knowledge about overall manufacturing tolerances like limitations in production or subsystems are not even completely defined. Furthermore, flexibility is required to handle new requirements and shifting preferences concerning single subsystems arising later in the development. Hence, a set-based approach using intervals for design variables (i.e., interaction quantities between subsystems and the total system) is useful. Because in the published approaches, no uncertainty consideration was taken into account for the computation of these intervals, they can possibly have inappropriate size, i.e., being too narrow. The work presented here proposes to include these uncertainties related to design variables. This allows now to consider lack-of-knowledge uncertainty specific for early phase developments in the framework of complex systems design. An example taken from a standard crash load case (frontal impact against a rigid wall) illustrates the proposed methodology.
Early-Stage Dynamics in Vascular Endothelial Cells Exposed to Hydrostatic Pressure
Authors: Yoshino Daisuke , Sato Masaaki
Published: June 2019

Blood pressure is an important factor both in maintaining body homeostasis and in its disruption. Vascular endothelial cells (ECs) are exposed to varying degrees of blood pressure and therefore play an important role in these physiological and pathological events. However, the effect of blood pressure on EC functions remains to be elucidated. In particular, we do not know how ECs sense and respond to changes in hydrostatic pressure even though the hydrostatic pressure is known to affect the EC functions. Here, we hypothesized that the cellular responses, leading to the reported pressure effects, occur at an early stage of pressure exposure and observed the early-stage dynamics in ECs to elucidate mechanisms through which ECs sense and respond to hydrostatic pressure. We found that exposure to hydrostatic pressure causes an early actomyosin-mediated contraction of ECs without a change in cell morphology. This response could be caused by water efflux from the ECs following exposure to hydrostatic pressure. Although only a limited study, these findings do explain a part of the mechanism through which ECs sense and respond to hydrostatic pressure.
A Novel Finite Element Model to Assess the Effect of Solid Stress Inside Tumors on Elastographic Normal Strains and Fluid Pressure
Authors: Islam Md Tauhidul , Righetti Raffaella
Published: June 2019

Ultrasound elastography is a noninvasive imaging modality used to assess the mechanical behavior of tissues, including cancers. Analytical and finite element (FE) models are useful and effective tools to understand the mechanical behavior of cancers and predict elastographic parameters under different testing conditions. A number of analytical and FE models to describe the mechanical behavior of cancers in elastography have been reported in the literature. However, none of these models consider the presence of solid stress (SS) inside the cancer, a clinically significant mechanical parameter with an influential role in cancer initiation, progression, and metastasis. In this paper, we develop an FE model applicable to cancers, which include both SS and elevated interstitial fluid pressure (IFP). This model is then used to assess the effects of these mechanical parameters on the normal strains and the fluid pressure, estimated using ultrasound poroelastography. Our results indicate that SS creates space-dependent changes in the strains and fluid pressure inside the tumor. This is in contrast to the effects produced by IFP on the strains and fluid pressure, which are uniformly distributed across the cancer. The developed model can help elucidating the role of SS on elastographic parameters and images. It may also provide a means to indirectly obtain information about the SS from the observed changes in the experimental elastographic images.
Predictors of Success of Workplace Physical Activity Interventions: A Systematic Review
Authors: Muir Samuel D. , Silva Sandun S.M. , Woldegiorgis Mulu A. , Rider Hayley , Meyer Denny , Jayawardana Madawa W.
Published: June 2019

Background: Despite holding great potential for addressing concerns regarding public health, recent systematic reviews have found effect sizes for interventions targeting physical activity to be small. Before interventions can be improved, the factors influencing outcomes must be identified. This systematic review aimed to identify predictors of success, measured in terms of engagement (eg, involvement duration) and health behavior change (eg, increased step counts), of workplace interventions targeting physical activity.Methods: A structured search of 3 databases (PubMed, PsycINFO, and Web of Science) was conducted to identify articles published between January 2000 and April 2017. For inclusion, articles needed to test a workplace intervention targeting physical activity and perform a quantitative analysis, identifying predictors of engagement or health behavior change.Results: Twenty-two studies were identified for review (median quality score = 70%). Demographic variables (eg, gender, age) were inconsistent predictors of success. However, employees in better health and physically active at baseline were found to have a greater likelihood of success.Conclusions: It appears that achieving successful results among employees at high risk of poor health outcomes remains a significant challenge for interventions. It is hoped that program developers can use this information to create effective interventions particularly for more sedentary employees.
Pulmonary fibrosis and embolism secondary to silicon implant leak
Authors: Azeem Ahad , Khuwaja Samreen , Parthvi Rukma , Persaud Teekaram
Published: June 2019

Pulmonary fibrosis in a patient with history of ruptured silicone breast implants may present a therapeutic challenge to diagnose and treat. In this case report, we aim to discuss our experience in diagnosing a patient with chronic silicone embolism syndrome masquerading as refractory multifocal pneumonia that presented with respiratory failure. A young woman with no significant past exposure having recurrent admissions to the hospital due to fever and shortness of breath was found to have chronic silicone embolism with pneumonitis. This case report emphasis the prompt diagnosis and treatment of silicone induced fibrosis and approach to the most common side effects of breast implants.
Compliance with needle-use declarations at two Olympic Winter Games: Sochi (2014) and PyeongChang (2018)
Authors: Schobersberger Wolfgang , Blank Cornelia , Budgett Richard , Pipe Andrew , Stuart Mark Campbell
Published: June 2019

Objectives

We describe compliance with the ‘IOC Needle Policy’ at two Winter Olympic Games (Sochi and PyeongChang) and compare these findings to those of the Summer Olympic Games of Rio de Janeiro.

Method

All needle-use declaration(s) (NUD) received during the course of the 2014 and 2018 Olympic Games were reviewed. We recorded socio-demographic data, the nature and purpose of needle use, product(s) injected, and route of administration. Data were analysed descriptively.

Results

In total, doctors from 22 National Olympic Committees (NOCs) submitted 122 NUD involving 82 athletes in Sochi; in PyeongChang, doctors from 19 NOCs submitted 82 NUD involving 61 athletes. This represented approximately 2% of all athletes at both Games, and 25% and 20% of all NOCs participating in Sochi and PyeongChang, respectively. No marked differences in the NUD distribution patterns were apparent when comparing the two Winter Olympic Games. The most commonly administered substances were as follows: local anaesthetics, non-steroidal anti-inflammatory drug and glucocorticoids. Physicians submitted multiple NUD for 24% of all athletes who required a NUD.

Conclusion

A limited number of NOCs submitted NUD suggesting a low incidence of needle use or limited compliance (approximately 2%). A key challenge for the future is to increase the rate of compliance in submitting NUD. More effective education of NOCs, team physicians and athletes regarding the NUD policy, its purpose, and the necessity for NUD submissions, in association with the enforcement of the appropriate sanctions following non-compliance are needed.
Towards resilient health systems: opportunities to align surgical and disaster planning
Authors: Pyda Jordan , Patterson Rolvix H , Caddell Luke , Wurdeman Taylor , Koch Rachel , Polatty David , Card Brittany , Meara John G , Corlew Daniel Scott
Published: June 2019

Natural disasters significantly contribute to human death and suffering. Moreover, they exacerbate pre-existing health inequalities by imposing an additional burden on the most vulnerable populations. Robust local health systems can greatly mitigate this burden by absorbing the extraordinary patient volume and case complexity immediately after a disaster. This resilience is largely determined by the predisaster local surgical capacity, with trauma, neurosurgical, obstetrical and anaesthesia care of particular importance. Nevertheless, the disaster management and global surgery communities have not coordinated the development of surgical systems in low/middle-income countries (LMIC) with disaster resilience in mind. Herein, we argue that an appropriate peridisaster response requires coordinated surgical and disaster policy, as only local surgical systems can provide adequate disaster care in LMICs.

We highlight three opportunities to help guide this policy collaboration. First, the Lancet Commission on Global Surgery and the Sendai Framework for Disaster Risk Reduction set forth independent roadmaps for global surgical care and disaster risk reduction; however, ultimately both advocate for health system strengthening in LMICs. Second, the integration of surgical and disaster planning is necessary. Disaster risk reduction plans could recognise the role of surgical systems in disaster preparedness more explicitly and pre-emptively identify deficiencies in surgical systems. Based on these insights, National Surgical, Obstetric, and Anesthesia Plans, in turn, can better address deficiencies in systems and ensure increased disaster resilience. Lastly, the recent momentum for national surgical planning in LMICs represents a political window for the integration of surgical policy and disaster risk reduction strategies.
Placement and sales of tobacco products and nicotine replacement therapy in tobacco-free and tobacco-selling pharmacies in Northern California: an observational study
Authors: Pimentel Liriany , Apollonio Dorie E
Published: June 2019

Objectives

Although tobacco is the leading preventable cause of death in the USA, it is routinely sold in pharmacies. In 2008, San Francisco became the first city in the USA to pass a tobacco-free pharmacy ordinance. Over the next decade, 171 municipalities enacted similar policies, and in 2018, Massachusetts banned tobacco sales in pharmacies. Our objective was to assess the perceived effects of tobacco-free pharmacy policies on displays, sales, customer visits and counselling.

Design

Observational study and survey.

Setting

In 2017, we visited Walgreens and CVS stores in San Francisco and nearby San Jose, which allows tobacco sales, to assess placement of tobacco and over-the-counter tobacco cessation products (nicotine replacement therapy or NRT). We surveyed an employee at each site regarding the impact that tobacco-free pharmacy policies had had on customer traffic and sales of NRT.

Participants

We obtained display data from 72 pharmacies and collected surveys from 55 employees (76% response rate).

Results

A majority of respondents at tobacco-free pharmacies (55%) reported that the policy had not affected customer visits. In comparison, 70% of respondents at tobacco-selling pharmacies believed that eliminating tobacco sales would reduce the number of customers visiting their stores. Pharmacies that were tobacco free and those that sold tobacco reported comparable displays, sales and counselling for NRT.

Conclusions

Pharmacies operating under tobacco-free policies did not report reduced customer visits. Greater awareness of this outcome could help pharmacies implement public health recommendations to eliminate tobacco sales.
DESKK Study - Development and testing of a dementia-specific respite care concept with a mobility and counselling programme: study protocol
Authors: Heinrich Steffen , Cavazzini Christoph , Holle Bernhard
Published: June 2019

Introduction

Specific mobility programmes can delay functional decline in people with dementia (PwD). Family caregivers (FCs) can be relieved from care-related burden by counselling services. Respite care is a short-term inpatient care service (1–8 weeks of stay). Respite care centres (RCCs) can function as support structures for dementia care arrangements through caring-based mobility training of PwD and counselling sessions for their FCs. However, no systematic mobility or counselling programmes exist in this setting in Germany or the rest of the world. The aim of the development and testing of a dementia-specific respite care concept (DESKK) study is the development and testing of an evidence-based mobility and counselling programme for PwD and their FCs that is suitable for the respite care setting.

Methods and analysis

A pilot-based, quasi-experimental evaluation study will be conducted in a specialised RCC for PwD. To evaluate the acceptance and usability of the development and testing of a DESKK concept, qualitative data will be collected from the RCC staff and FCs via semistandardised interviews. Quantitative data will be collected using instruments to assess effect tendencies of the concept related to mobility (PwD) and burden (FCs). Furthermore, a mixed-methods triangulation approach will be conducted.

Ethics and dissemination

The protocol, informed consent and accompanying material given to patients were submitted by the investigator to the Ethical Review Committee of the German Society of Nursing Science. The project was examined and finally approved on 31 January 2017 (Number: 16–27). Prior to obtaining written consent for study participation, information must be given to all of the study participants in verbal and written form. The results of the study will be presented at national and international conferences and published in peer-reviewed journals. After the concept is finalised, a practice-friendly manual will be developed in which implementation components are described for other RCCs.

Trial registration number

NCT03578861
Does the Patient-Reported Apnea Questionnaire (PRAQ) increase patient-centredness in the daily practice of sleep centres? a mixed-methods study
Authors: Abma Inger L , Rovers Maroeska M , IJff Marijke , Hol Bernard , Nägele Masha , Westert Gert P , van der Wees Philip J
Published: June 2019

Objectives

The objective of this exploratory study was to see how the Patient-Reported Apnea Questionnaire (PRAQ) may impact the daily clinical practice of sleep centres, and why it may or may not work as expected. The hypotheses were tested that this patient-reported outcome measure makes patients more aware of which of their health complaints may be related to obstructive sleep apnoea (OSA), and that it improves patient-centredness of care by shifting the focus of care away from (only) medical problems towards the individual burden of disease and quality of life.

Design

Mixed methods. The quantitative study (surveys, patient records) was a before-and-after study.

Setting

Three sleep centres in The Netherlands (secondary care).

Participants

27 patients and 14 healthcare professionals were interviewed. 487 patients completed surveys pre-implementation, and 377 patients completed surveys post-implementation of the PRAQ. For the health records, 125 patients were included in the pre-implementation group, and 124 other patients in the post-implementation group.

Interventions

The PRAQ was used in clinical practice for six successive months.

Outcome measures

Scores on individual survey items, number of patients receiving non-medical treatment, adjustment of treatment at first follow-up, compliance with treatment.

Results

Patients were generally positive about the usefulness of the PRAQ before and during the consultation, as they felt more informed. Healthcare providers did not consider the PRAQ very useful, and they reported minor impact on their consultations. The surveys and health record study did not show an impact of the PRAQ on clinical practice.

Conclusions

Implementing the PRAQ may be beneficial to patients, but this study does not show much impact with regard to patient-centredness of care. New Dutch guidelines for OSA care may lead to a greater emphasis on quality of life and value of care for patients, making its integration in clinical care potentially more useful.
Trends in the receipt of medicines information among Finnish adults in 1999–2014: a nationwide repeated cross-sectional survey
Authors: Mononen Niina , Airaksinen Marja S A , Hämeen-Anttila Katri , Helakorpi Satu , Pohjanoksa-Mäntylä Marika
Published: June 2019

Objective

The aim of this study was to examine long-term trends in the receipt of medicines information (MI) among adult medicine users from 1999 to 2014.

Design

Repeated cross-sectional postal survey from the years 1999, 2002, 2005 and 2008–2014.

Setting

Each study year, a new nationally representative sample of 5000 Finns aged 15–64 years was drawn from the Population Register Centre of Finland.

Participants

The range of annual respondents varied from 2545 to 3371 and response rates from 53% to 67%. Of the total responses (n=29 465), 64% were from medicine users (n=18 862, ranging by year from 58% to 68%).

Outcome measures

Receipt of information on medicines in use within 12 months prior to the survey from a given list of consumer MI sources available in Finland.

Results

Physicians, community pharmacists and package leaflets were the most common MI sources throughout the study period. Receipt of MI increased most from the Internet (from 1% in 1999 to 16% in 2014), while decreased most from physicians (62% to 47%) and package leaflets (44% to 34%), and remained stable from community pharmacists (46% to 45%) and nurses (14% to 14%). In 1999, of the medicine users 4% did not report receipt of MI from any of the sources listed in the survey, while this proportion had remarkably increased to 28% in 2014.

Conclusions

Healthcare professionals and package leaflets had still a dominating importance in 2014 despite the growing number of MI sources over time, but still a minority of adult medicine users reported receiving MI via the Internet in 2014. Worrying is that the proportion of adult medicine users who did not receive MI from any of the sources became seven fold during the study period.
Does a simple web-based intervention facilitate the articulation of patients’ unvoiced agenda for a consultation with their diabetologists? A qualitative study
Authors: Frost Julia , Gibson Andy , Ukoumunne Obioha , Vaidya Bijay , Britten Nicky
Published: June 2019

Objective

To explore whether a preconsultation web-based intervention enables patients with diabetes to articulate their agenda in a consultation in the hospital outpatient clinic with their diabetologist.

Methods and design

A qualitative study embedded in a pragmatic pilot randomised controlled trial.

Setting

Two city outpatient departments in England.

Participants

25 patients attending a follow-up consultation and 6 diabetologists.

Intervention

The PACE-D, a web-based tool adapted for patients with diabetes to use before their consultation to generate an agenda of topics to discuss with their diabetologist.

Data collection

25 participants had their consultation with their diabetologist audio-recorded: 12 in the control arm and 13 in the intervention arm; 12 of the latter also had their PACE-D intervention session and a consultation recorded. Semi-structured interviews with 6 diabetologists, and 12 patients (6 in the intervention group and 6 in the control group).

Analysis

Thematic discourse analysis undertaken with patient representatives trained in qualitative data analysis techniques.

Results

We identified four consultation types: diabetologist facilitated; patient identified; consultant facilitated and patient initiated and patient ignored. We also identified three critical aspects that explained the production and utilisation of the agenda form: existing consultative style; orientation to the use of the intervention and impact on the consultation. Where patients and diabetologists have a shared preference for a consultant-led or patient-led consultation, the intervention augments effective communication and shared decision making. However, where preferences diverge (eg, there is a mismatch in patients' and diabetologists' preferences and orientations), the intervention does not improve the potential for shared decision making.

Conclusion

A simple web-based intervention facilitates the articulation of patients’ unvoiced agenda for a consultation with their diabetologist, but only when pre-existing consultation styles and orientations already favour shared decision making. More needs to be done to translate patient empowerment in the consultation setting into genuine self-efficacy.

Trial registration number

ISRCTN75070242.
Molidustat for the treatment of renal anaemia in patients with dialysis-dependent chronic kidney disease: design and rationale of three phase III studies
Authors: Akizawa Tadao , Taguchi Megumi , Matsuda Yoshimi , Iekushi Kazuma , Yamada Takashi , Yamamoto Hiroyasu
Published: June 2019

Introduction

New medications for anaemia associated with chronic kidney disease (CKD) are desirable, owing to the limitations of erythropoiesis-stimulating agents (ESAs), the current standard of care. Molidustat is a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor that stimulates erythropoietin production, predominately in the kidney. We report methodological details of three phase III trials, named MolIdustat once dailY improves renal Anaemia By Inducing erythropoietin (MIYABI), designed primarily to investigate the efficacy of molidustat therapy in adults with renal anaemia and dialysis-dependent CKD.

Methods and analysis

MIYABI Haemodialysis-Correction (HD-C) is a single-arm trial (24-week treatment duration) in approximately 25 patients on haemodialysis, currently untreated with ESAs. MIYABI Peritoneal Dialysis (PD) is a single-arm trial (36 week treatment duration) in approximately 50 patients on peritoneal dialysis, treated or untreated with ESAs. MIYABI Haemodialysis-Maintenance (HD-M) is a randomised, active-controlled, double-blinded, double-dummy trial (52-week treatment duration) comparing molidustat with darbepoetin alfa in approximately 225 patients on haemodialysis, treated with ESAs. Molidustat (starting dose 75 mg/day) will be titrated 4-weekly to maintain haemoglobin in predetermined target ranges. The primary objective is to evaluate the efficacy of molidustat, using the following measures: the rate of rise in haemoglobin (g/L/week) at the first dose change up to week 8 (MIYABI HD-C); responder rate (MIYABI HD-C and MIYABI PD); mean haemoglobin level during weeks 33–36 and non-inferiority to darbepoetin alfa shown by change in mean haemoglobin level from baseline (MIYABI HD-M). The secondary objectives are to assess safety, pharmacokinetics and pharmacodynamics. These trials will provide the first evaluations of molidustat therapy in patients receiving either peritoneal dialysis or currently untreated with ESAs on haemodialysis, and provide further evidence in patients treated with ESAs on haemodialysis.

Ethics and dissemination

The protocols were approved by ethics committees at all participating sites. The trials will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results arising from these studies will be published in peer-reviewed journal(s).

Trial registration numbers

NCT03351166; Pre-results,NCT03418168; Pre-results,NCT03543657; Pre-results
Molidustat for the treatment of renal anaemia in patients with non-dialysis-dependent chronic kidney disease: design and rationale of two phase III studies
Authors: Yamamoto Hiroyasu , Taguchi Megumi , Matsuda Yoshimi , Iekushi Kazuma , Yamada Takashi , Akizawa Tadao
Published: June 2019

Introduction

Anaemia is a common complication of chronic kidney disease (CKD). Owing to the limitations of erythropoiesis-stimulating agents (ESAs), the current standard of care, there is a need to develop new therapies. Hypoxia-inducible factor prolyl-hydroxylase (HIF-PH) inhibitors might be a promising new treatment option. Molidustat is an oral HIF-PH inhibitor that stimulates the endogenous, predominantly renal, production of erythropoietin and was generally well tolerated in phase IIb clinical trials. Here, we report the design and rationale of two studies from the molidustat phase III programme: MolIdustat once dailY improves renal Anaemia By Inducing erythropoietin (MIYABI).

Methods and analysis

MIYABI Non-Dialysis-Correction (ND-C) and MIYABI Non-Dialysis-Maintenance (ND-M) are randomised, open-label, parallel-group, multicentre studies that aim to demonstrate the efficacy of molidustat treatment compared with darbepoetin alfa in patients with anaemia and non-dialysis-dependent CKD. The secondary objectives are to assess the safety, pharmacokinetics and pharmacodynamics of molidustat treatment. MIYABI ND-C will recruit patients currently untreated with ESAs, whereas patients treated with an ESA will enter MIYABI ND-M. Each study will recruit 150 patients who will be randomised in a 1:1 ratio to receive either molidustat or darbepoetin alfa for 52 weeks, with efficacy evaluated during weeks 30–36. Study drug doses will be titrated regularly using an interactive voice/web response system with the aim of maintaining the patients’ haemoglobin (Hb) levels between ≥110 and <130 g/L. The primary objective will be achieved if, in molidustat-treated patients, the mean Hb level remains within the target range during the evaluation period, and if the change in the mean Hb level at evaluation time points from baseline is non-inferior to darbepoetin alfa.

Ethics and dissemination

The protocols were approved by ethics committees at all participating sites. These studies will be conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice guidelines. Results arising from these studies will be published in peer-reviewed journal(s).

Trial registration numbers

NCT03350321; Pre-results,NCT03350347; Pre-results.
Exercise referral schemes enhanced by self-management strategies to reduce sedentary behaviour and increase physical activity among community-dwelling older adults from four European countries: protocol for the process evaluation of the SITLESS randomised controlled trial
Authors: Coll-Planas Laura , Blancafort Alias Sergi , Tully Mark , Caserotti Paolo , Giné-Garriga Maria , Blackburn Nicole , Skjødt Mathias , Wirth Katharina , Deidda Manuela , McIntosh Emma , Rothenbacher Dietrich , Gallardo Rodríguez Rodrigo , Jerez-Roig Javier , Sansano-Nadal Oriol , Santiago Marta , Wilson Jason , Guerra-Balic Míriam , Martín-Borràs Carme , Gonzalez Denise , Lefebvre Guillaume , Denkinger Michael , Kee Frank , Salvà Casanovas Antoni , Roqué i Figuls Marta
Published: June 2019

Introduction

SITLESS is a randomised controlled trial determining whether exercise referral schemes can be enhanced by self-management strategies to reduce sedentary behaviour and increase physical activity in the long term, in community-dwelling older citizens. The intervention is complex and requires a process evaluation to understand how implementation, causal mechanisms and context shape outcomes. The specific aims are to assess fidelity and reach of the implementation, understand the contextual aspects of each intervention site, evaluate the mechanisms of impact, and explore perceived effects.

Methods and analysis

Following the Medical Research Council guidance on complex interventions, a combination of qualitative and quantitative procedures is applied, including observational checklists and attendance registries, standardised scales (ie, Marcus’s Self-Efficacy Questionnaire, Physical Activity Self-Regulation Scale and the Lubben Social Network Scale) at baseline, postintervention and follow-up assessments, semistructured questionnaires gathering contextual characteristics, and participant observations of the sessions. Semistructured interviews and focus groups with the participants and trainers are conducted at postintervention and during the follow-up to explore their experiences. Outcomes from the standardised scales are analysed as moderators within the impact evaluation. Descriptive results on context and perceived effects complement results on impact. The qualitative and quantitative findings will help to refine the logic model to finally support the interpretation of the results on the effectiveness of the intervention.

Ethics and dissemination

The study design was approved by the respective Ethical Committee of Ramon Llull University, Southern Denmark, Northern Ireland and Ulm University. Participation is voluntary, and all participants are asked to sign informed consent before starting the study. A dissemination plan operationalises how to achieve a social impact by reaching academic and non-academic stakeholders. A data management plan describes the specific data sets and regulates its deposition and curation. All publications will be open access.

Trial registration number

NCT02629666; Pre-results.
Health behaviours and mental and physical health status in older adults with a history of homelessness: a cross-sectional population-based study in England
Authors: Smith Lee , Veronese Nicola , López-Sánchez Guillermo Felipe , Moller Eloise , Johnstone James , Firth Joseph , Grabovac Igor , Yang Lin , Soysal Pinar , Jackson Sarah E
Published: June 2019

Objectives

This study compared (1) levels of engagement in lifestyle risk behaviours and (2) mental and physical health status in individuals who have previously been homeless to those of individuals who have not.

Design

Cross-sectional.

Participants

Data were from participants (n=6931) of the English Longitudinal Study of Ageing.

Measures

Participants reported whether they had ever been homeless. We used regression models to analyse associations between homelessness and (1) cigarette smoking, daily alcohol consumption and physical inactivity, adjusting for sociodemographic covariates (age, sex, ethnicity, highest level of education, marital status and household non-pension wealth) and (2) self-rated health, limiting long-standing illness, depressive symptoms, life satisfaction, quality of life and loneliness, adjusting for sociodemographics and health behaviours.

Results

104 participants (1.5%) reported having been homeless. Individuals who had been homeless were significantly more likely to be physically inactive (OR 1.62, 95% CI 1.44 to 2.52), report fair/bad/very bad self-rated health (OR 1.75, 95% CI 1.07 to 2.86), have a limiting long-standing illness (OR 2.66, 95% CI 1.65 to 4.30) and be depressed (OR 3.06, 95% CI 1.85 to 5.05) and scored lower on measures of life satisfaction (17.34 vs 19.96, p<0.001) and quality of life (39.02 vs 41.21, p=0.013). Rates of smoking (20.2% vs 15.4%, p=0.436), daily drinking (27.6% vs 22.8%, p=0.385) and loneliness (27.1% vs 21.0%, p=0.080) were also elevated.

Conclusions

Those who were once homeless have poorer mental and physical health outcomes and are more likely to be physically inactive. Interventions to improve their health and quality of life are required.
Endoscopic ultrasound versus endoscopic retrograde cholangiopancreatography-guided biliary drainage for primary decompression of malignant biliary obstruction: protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Jin Zheng , Wei Yaping , Lin Huapeng , Huang Haitao , Lv Wen , Zhang Xiaofeng
Published: June 2019

Introduction

Current evidence supporting the utility of endoscopic ultrasound-guided biliary drainage (EUS-BD) as a first-line treatment option for malignant biliary obstruction (MBO) is limited. We plan to provide a systematic review and meta-analysis to compare the performance of EUS-BD and endoscopic retrograde cholangiopancreatography-guided biliary drainage (ERCP-BD) as primary palliation of MBO.

Methods and analysis

Randomised controlled trials evaluating EUS-BD versus ERCP-BD in primary drainage of MBO will be searched in MEDLINE, EMBASE, Web of Science, the Cochrane Library, ClinicalTrials.gov and Google Scholar, from database inception to 31 October 2018. Data on study design, participant characteristics, intervention details and outcomes will be extracted. Primary outcomes to be assessed are technical and clinical success. Secondary outcomes include adverse events, stent patency, stent dysfunction, reinterventions, procedure duration and overall survival. Study quality will be assessed using the Cochrane Risk of Bias Tool. Meta-analysis will be performed using RevMan V.5.3 statistical software. Data will be combined with a random effect model. The results will be presented as a risk ratio for dichotomous data, weighted mean difference for continuous data and HR for time-to-event data. Publication bias will be visualised using funnel plots.

Ethics and dissemination

This study will not use primary data, and therefore, formal ethical approval is not required. The findings will be disseminated through peer-reviewed journals and committee conferences.

PROSPERO registration number

CRD42018117040
Factors supporting and constraining the implementation of robot-assisted surgery: a realist interview study
Authors: Randell Rebecca , Honey Stephanie , Alvarado Natasha , Greenhalgh Joanne , Hindmarsh Jon , Pearman Alan , Jayne David , Gardner Peter , Gill Arron , Kotze Alwyn , Dowding Dawn
Published: June 2019

Objective

To capture stakeholders’ theories concerning how and in what contexts robot-assisted surgery becomes integrated into routine practice.

Design

A literature review provided tentative theories that were revised through a realist interview study. Literature-based theories were presented to the interviewees, who were asked to describe to what extent and in what ways those theories reflected their experience. Analysis focused on identifying mechanisms through which robot-assisted surgery becomes integrated into practice and contexts in which those mechanisms are triggered.

Setting

Nine hospitals in England where robot-assisted surgery is used for colorectal operations.

Participants

Forty-four theatre staff with experience of robot-assisted colorectal surgery, including surgeons, surgical trainees, theatre nurses, operating department practitioners and anaesthetists.

Results

Interviewees emphasised the importance of support from hospital management, team leaders and surgical colleagues. Training together as a team was seen as beneficial, increasing trust in each other’s knowledge and supporting team bonding, in turn leading to improved teamwork. When first introducing robot-assisted surgery, it is beneficial to have a handpicked dedicated robotic team who are able to quickly gain experience and confidence. A suitably sized operating theatre can reduce operation duration and the risk of de-sterilisation. Motivation among team members to persist with robot-assisted surgery can be achieved without involvement in the initial decision to purchase a robot, but training that enables team members to feel confident as they take on the new tasks is essential.

Conclusions

We captured accounts of how robot-assisted surgery has been introduced into a range of hospitals. Using a realist approach, we were also able to capture perceptions of the factors that support and constrain the integration of robot-assisted surgery into routine practice. We have translated these into recommendations that can inform future implementations of robot-assisted surgery.
Can we validate a clinical score to predict the risk of severe infection in patients with systemic lupus erythematosus? A longitudinal retrospective study in a British Cohort
Authors: Tejera Segura Beatriz , Rua-Figueroa Iñigo , Pego-Reigosa Jose Maria , del Campo Victor , Wincup Chris , Isenberg David , Rahman Anisur
Published: June 2019

Objective

Severe infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Our primary objective was to use data from a large Spanish cohort to develop a risk score for severe infection in SLE, the SLE Severe Infection Score (SLESIS) and to validate SLESIS in a separate cohort of 699 British patients.

Design and setting

Retrospective longitudinal study in a specialist tertiary care clinic in London, UK.

Participants

Patients fulfilling international classification criteria for SLE (n=209). This included 98 patients who had suffered severe infections (defined as infection leading to hospitalisation and/or death) and 111 randomly selected patients who had never suffered severe infections.

Outcomes

We retrospectively calculated SLESIS at diagnosis for all 209 patients. For the infection cases we also calculated SLESIS just prior to infection and compared it to SLESIS in 98 controls matched for disease duration. We carried out receiver operator characteristic (ROC) analysis to quantify predictive value of SLESIS for severe infection.

Results

Median SLESIS (IQR) at diagnosis was higher in the infection group than in the control group (4.27 (3.18) vs 2.55 (3.79), p=0.0008). Median SLESIS prior to infection was higher than at diagnosis (6.64 vs 4.27, p<0.001). In ROC analysis, predictive value of SLESIS just before the infection (area under the curve (AUC)=0.79) was higher than that of SLESIS at diagnosis (AUC=0.63).

Conclusions

We validated the association of SLESIS with severe infection in an independent cohort. Calculation of SLESIS at each clinic visit may help in management of infection risk in patients with SLE. Prospective studies are needed to confirm these findings.