bluuebunny/crossref_metadata_2025 huggingface dataset:
Reframing Finance
Authors: Monk Ashby , Sharma Rajiv , Sinclair Duncan L.
Published: January 2018

The role of financial intermediaries has come under close scrutiny in recent times as many of the practices of these service firms have been exposed for their opaque, rent-seeking and dishonest behavior. This book questions the traditional system of Financial Capitalism by examining how beneficiary organizations such as pension funds, sovereign wealth funds, endowments and foundations can reduce the inefficiencies of intermediaries in the savings-investment channel. This book argues that the large pools of long-term capital held in beneficiary organizations has not been mobilized efficiently enough into the capital-intensive long-term projects such as infrastructure, green energy, agriculture, private equity and real estate development. In particular, the book examines a new ‘collaborative’ form of investing that a large number of beneficiary organizations have started to embark on in order to address the problem of mainstream financial intermediation and achieve their long-term investment objectives. The book conceptualizes the ‘collaborative’ model of investment, drawing upon economic sociology, and emphasizes the importance for investors to build their social capital. By providing case study exemplars of collaborative vehicles such as co-investment platforms, joint ventures, and platform companies that invest in infrastructure, agriculture, private equity and real estate, the book provides useful insights for how long-term investment management might be shaped in the future.
Vacuum furnace for degassing stainless-steel vacuum components
Authors: Fedchak James A. , Scherschligt Julia , Barker Daniel , Eckel Stephen , Farrell Alex P. , Sefa Makfir
Published: January 2018

Ultrahigh vacuum systems must often be constructed of materials with ultralow outgassing rates to achieve pressure of 10−6 Pa and below. Any component placed into the ultrahigh vacuum system must also be constructed of materials with ultralow outgassing rates. Baking stainless steel vacuum components to a temperature range of 400–450 °C while under vacuum is an effective method to reduce the outgassing rate of vacuum components for use in ultrahigh vacuum systems. The design, construction, and operation of a vacuum furnace capable of baking vacuum components to a temperature of 450 °C while maintaining a pressure of 10−3 Pa or lower is described. The furnace has been used for extended bakes at 450 °C while maintaining pressures below 10−5 Pa. As an example, the authors obtained an outgassing rate of 1.2 × 10−9 Pa l s−1 for a gate valve baked for 20 days at a temperature of 420 °C.
Pile driving acoustics made simple: Damped cylindrical spreading model
Authors: Lippert Tristan , Ainslie Michael A. , von Estorff Otto
Published: January 2018

Sound produced by marine pile driving activities poses a possible risk to marine life. The assessment and mitigation of this risk requires a precise prediction of the expected levels. An analytical approach to estimate the radiated sound exposure levels is presented, based on the axial symmetry of the problem, resulting in damped cylindrical spreading. The approach is verified against numerical results from the recently held COMPILE benchmark workshop and validated with data from three different wind farm construction sites in the North Sea. In addition, found to yield more accurate estimates of the sound exposure level than an empirical decay formula sometimes used to evaluate the impact of marine pile driving.
Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass
Authors: Alqahtani Saeed A. , Alsultan Abdullah S. , Alqattan Hussain M. , Eldemerdash Ahmed , Albacker Turki B.
Published: January 2018

The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CL
CR
). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval (
fT
MIC
) of 65% for an MIC of 8 mg/liter in patients with a CL
CR
of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CL
CR
of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CL
CR
values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CL
CR
values (≤30 ml/min).
An Archaeal Fluoride-Responsive Riboswitch Provides an Inducible Expression System for Hyperthermophiles
Authors: Speed Michael Clayton , Burkhart Brett W. , Picking Jonathan W. , Santangelo Thomas J.
Published: January 2018

Robust genetic systems for the hyperthermophilic
Thermococcales
have facilitated the overexpression of native genes, enabled the addition of sequences encoding secretion signals, epitope, and affinity tags to coding regions, and aided the introduction of sequences encoding new proteins in these fast-growing fermentative heterotrophs. However, tightly controlled and easily manipulated systems facilitating regulated gene expression are limited for these hosts. Here, we describe an alternative method for regulatory control reliant on a
cis
-encoded functional riboswitch in the model archaeon
Thermococcus kodakarensis
. Despite the hyperthermophilic growth temperatures, the proposed structure of the riboswitch conforms to a fluoride-responsive riboswitch encoded in many bacteria and similarly functions to regulate a component-conserved fluoride export pathway. Deleting components of the fluoride export pathway generates
T. kodakarensis
strains with increased fluoride sensitivity. The mechanism underlying regulated expression suggested that the riboswitch-encoding sequences could be utilized as a tunable expression cassette. When appended to a reporter gene, the riboswitch-mediated control system provides fluoride-dependent tunable regulatory potential, offering an alternative system for regulating gene expression. Riboswitch-regulated expression is thus ubiquitous in extant life and can be exploited to generate regulated expression systems for hyperthermophiles.

IMPORTANCE
Gene expression is controlled by a myriad of interconnected mechanisms that interpret metabolic states and environmental cues to balance cell physiology. Transcription regulation in
Archaea
is known to employ both typical repressors-operators and transcription activators to regulate transcription initiation in addition to the regulation afforded by chromatin structure. It was perhaps surprising that the presumed ancient mechanism of riboswitch-mediated regulation is found in
Bacteria
and
Eukarya
, but seemingly absent in
Archaea
. We demonstrate here that a fluoride-responsive riboswitch functions to regulate a detoxification pathway in the hyperthermophilic archaeon
Thermococcus kodakarensis
. The results obtained define a universal role for riboswitch-mediated regulation, adumbrate the presence of several riboswitch-regulated genes in
Thermococcus kodakarensis
, demonstrate the utility of RNA-based regulation at high temperatures, and provide a novel riboswitch-regulated expression system to employ in hyperthermophiles.
Cryptic Production of
trans
-3-Hydroxyproline in Echinocandin B Biosynthesis
Authors: Mattay Johanna , Houwaart Stefanie , Hüttel Wolfgang
Published: January 2018

Echinocandins are antifungal nonribosomal hexapeptides produced by fungi. Two of the amino acids are hydroxy-
l
-prolines:
trans
-4-hydroxy-
l
-proline and, in most echinocandin structures, (
trans
-2,3)-3-hydroxy-(
trans
-2,4)-4-methyl-
l
-proline. In the case of echinocandin biosynthesis by
Glarea lozoyensis
, both amino acids are found in pneumocandin A
0
, while in pneumocandin B
0
the latter residue is replaced by
trans
-3-hydroxy-
l
-proline (3-Hyp). We have recently reported that all three amino acids are generated by the 2-oxoglutarate-dependent proline hydroxylase GloF. In echinocandin B biosynthesis by
Aspergillus
species, 3-Hyp derivatives have not been reported. Here we describe the heterologous production and kinetic characterization of HtyE, the 2-oxoglutarate-dependent proline hydroxylase from the echinocandin B biosynthetic cluster in
Aspergillus pachycristatus
. Surprisingly,
l
-proline hydroxylation with HtyE resulted in an even higher proportion (∼30%) of 3-Hyp than that with GloF. This suggests that the selectivity for methylated 3-Hyp in echinocandin B biosynthesis is due solely to a substrate-specific adenylation domain of the nonribosomal peptide synthetase. Moreover, we observed that one product of HtyE catalysis, 3-hydroxy-4-methyl-
l
-proline, is slowly further oxidized at the methyl group, giving 3-hydroxy-4-hydroxymethyl-
l
-proline, upon prolonged incubation with HtyE. This dihydroxylated amino acid has been reported as a building block of cryptocandin, an echinocandin produced by
Cryptosporiopsis
.

IMPORTANCE
Secondary metabolites from bacteria and fungi are often produced by sets of biosynthetic enzymes encoded in distinct gene clusters. Usually, each enzyme catalyzes one biosynthetic step, but multiple reactions are also possible. Pneumocandins A
0
and B
0
are produced by the fungus
Glarea lozoyensis
. They belong to the echinocandin family, a group of nonribosomal cyclic lipopeptides that exhibit a strong antifungal activity. Chemical derivatives are important drugs for the treatment of systemic fungal infections. We have recently shown that in the biosynthesis of pneumocandins A
0
and B
0
, three hydroxyproline building blocks are provided by one proline hydroxylase. Here we demonstrate that the proline hydroxylase from echinocandin B biosynthesis in
Aspergillus pachycristatus
produces the same hydroxyprolines, with an increased proportion of
trans
-3-hydroxyproline. However, echinocandin B biosynthesis does not require
trans
-3-hydroxyproline; its formation remains cryptic. While one can only speculate on the evolutionary background of this unexpected finding, proline hydroxylation in
G. lozoyensis
and
A. pachycristatus
provides an unusual insight into peptide antibiotic biosynthesis—namely, the complex interplay between the selectivity of a hydroxylase and the substrate specificity of a nonribosomal peptide synthetase.
Are Phage Lytic Proteins the Secret Weapon To Kill
Staphylococcus aureus
?
Authors: Gutiérrez Diana , Fernández Lucía , Rodríguez Ana , García Pilar
Published: January 2018

Methicillin-resistant
Staphylococcus aureus
(MRSA) is one of the most threatening microorganisms for global human health. The current strategies to reduce the impact of
S. aureus
include a restrictive control of worldwide antibiotic use, prophylactic measures to hinder contamination, and the search for novel antimicrobials to treat human and animal infections caused by this bacterium. The last strategy is currently the focus of considerable research. In this regard, phage lytic proteins (endolysins and virion-associated peptidoglycan hydrolases [VAPGHs]) have been proposed as suitable candidates. Indeed, these proteins display narrow-spectrum antimicrobial activity and a virtual lack of bacterial-resistance development. Additionally, the therapeutic use of phage lytic proteins in
S. aureus
animal infection models is yielding promising results, showing good efficacy without apparent side effects. Nonetheless, human clinical trials are still in progress, and data are not available yet. This minireview also analyzes the main obstacles for introducing phage lytic proteins as human therapeutics against
S. aureus
infections. Besides the common technological problems derived from large-scale production of therapeutic proteins, a major setback is the lack of a proper legal framework regulating their use. In that sense, the relevant health authorities should urgently have a timely discussion about these new antimicrobials. On the other hand, the research community should provide data to dispel any doubts regarding their efficacy and safety. Overall, the appropriate scientific data and regulatory framework will encourage pharmaceutical companies to invest in these promising antimicrobials.
Adaptive Evolution of RH5 in Ape
Plasmodium
species of the
Laverania
Subgenus
Authors: Plenderleith Lindsey J. , Liu Weimin , MacLean Oscar A. , Li Yingying , Loy Dorothy E. , Sundararaman Sesh A. , Bibollet-Ruche Frederic , Learn Gerald H. , Hahn Beatrice H. , Sharp Paul M.
Published: January 2018

Plasmodium falciparum
, the major cause of malaria morbidity and mortality in humans, has been shown to have emerged after cross-species transmission of one of six host-specific parasites (subgenus
Laverania
) infecting wild chimpanzees (
Pan troglodytes
) and western gorillas (
Gorilla gorilla
). Binding of the parasite-encoded ligand RH5 to the host protein basigin is essential for erythrocyte invasion and has been implicated in host specificity. A recent study claimed to have found two amino acid changes in RH5 that “drove the host shift leading to the emergence of
P. falciparum
as a human pathogen.” However, the ape
Laverania
data available at that time, which included only a single distantly related chimpanzee parasite sequence, were inadequate to justify any such conclusion. Here, we have investigated
Laverania Rh5
gene evolution using sequences from all six ape parasite species. Searching for gene-wide episodic selection across the entire
Laverania
phylogeny, we found eight codons to be under positive selection, including three that correspond to contact residues known to form hydrogen bonds between
P. falciparum
RH5 and human basigin. One of these sites (residue 197) has changed subsequent to the transmission from apes to humans that gave rise to
P. falciparum
, suggesting a possible role in the adaptation of the gorilla parasite to the human host. We also found evidence that the patterns of nucleotide polymorphisms in
P. falciparum
are not typical of
Laverania
species and likely reflect the recent demographic history of the human parasite.

IMPORTANCE
A number of closely related, host-specific malaria parasites infecting wild chimpanzees and gorillas have recently been described. The most important cause of human malaria,
Plasmodium falciparum
, is now known to have resulted from a cross-species transmission of one of the gorilla parasites. Overcoming species-specific interactions between a parasite ligand, RH5, and its receptor on host cells, basigin, was likely an important step in the origin of the human parasite. We have investigated the evolution of the
Rh5
gene and found evidence of adaptive changes during the diversification of the ape parasite species at sites that are known to form bonds with human basigin. One of these changes occurred at the origin of
P. falciparum
, implicating it as an important adaptation to the human host.
Abiotic Stresses Shift Belowground
Populus
-Associated Bacteria Toward a Core Stress Microbiome
Authors: Timm Collin M. , Carter Kelsey R. , Carrell Alyssa A. , Jun Se-Ran , Jawdy Sara S. , Vélez Jessica M. , Gunter Lee E. , Yang Zamin , Nookaew Intawat , Engle Nancy L. , Lu Tse-Yuan S. , Schadt Christopher W. , Tschaplinski Timothy J. , Doktycz Mitchel J. , Tuskan Gerald A. , Pelletier Dale A. , Weston David J.
Published: January 2018

The identification of a common “stress microbiome” indicates tightly controlled relationships between the plant host and bacterial associates and a conserved structure in bacterial communities associated with poplar trees under different growth conditions. The ability of the microbiome to buffer the plant from extreme environmental conditions coupled with the conserved stress microbiome observed in this study suggests an opportunity for future efforts aimed at predictably modulating the microbiome to optimize plant growth.
Identifying patients at risk of inhospital death or hospice transfer for early goals of care discussions in a US referral center: the HELPS model derived from retrospective data
Authors: Romero-Brufau Santiago , Whitford Daniel , Whitford Kevin J , Manning Dennis M , Huddleston Jeanne M
Published: January 2018

Objective

Create a score to identify patients at risk of death or hospice placement who may benefit from goals of care discussion earlier in the hospitalisation.

Design

Retrospective cohort study to develop a risk index using multivariable logistic regression.

Setting

Two tertiary care hospitals in Southeastern Minnesota.

Participants

92 879 adult general care admissions (50% male, average age 60 years).

Primary and secondary outcome measures

Our outcome measure was an aggregate of inhospital death or discharge to hospice. Predictor variables for the model encompassed comorbidities, nutrition status, functional status, demographics, fall risk, mental status, Charlson Comorbidity Index and acuity of illness on admission. Resuscitation status, race, geographic area of residence and marital status were added as covariates to account for confounding.

Results

Inhospital mortality and discharge to hospice were rare, with incidences of 1.2% and 0.8%, respectively. The Hospital End-of-Life Prognostic Score (HELPS) demonstrated good discrimination (C-statistic=0.866 in derivation set and 0.834 in validation set). The patients with the highest 5% of scores had an 8% risk of the outcome measure, relative risk 12.9 (10.9–15.4) when compared to the bottom 95%.

Conclusions

HELPS is able to identify patients with a high risk of inhospital death or need for hospice at discharge. These patients may benefit from early goals of care discussions.
Evaluating dengue burden in Africa in passive fever surveillance and seroprevalence studies: protocol of field studies of the Dengue Vaccine Initiative
Authors: Lim Jacqueline Kyungah , Carabali Mabel , Lee Jung-Seok , Lee Kang-Sung , Namkung Suk , Lim Sl-Ki , Ridde Valéry , Fernandes Jose , Lell Bertrand , Matendechero Sultani Hadley , Esen Meral , Andia Esther , Oyembo Noah , Barro Ahmed , Bonnet Emmanuel , Njenga Sammy M , Agnandji Selidji Todagbe , Yaro Seydou , Alexander Neal , Yoon In-Kyu
Published: January 2018

Introduction

Dengue is an important and well-documented public health problem in the Asia-Pacific and Latin American regions. However, in Africa, information on disease burden is limited to case reports and reports of sporadic outbreaks, thus hindering the implementation of public health actions for disease control. To gather evidence on the undocumented burden of dengue in Africa, epidemiological studies with standardised methods were launched in three locations in Africa.

Methods and analysis

In 2014–2017, the Dengue Vaccine Initiative initiated field studies at three sites in Ouagadougou, Burkina Faso; Lambaréné, Gabon and Mombasa, Kenya to obtain comparable incidence data on dengue and assess its burden through standardised hospital-based surveillance and community-based serological methods. Multidisciplinary measurements of the burden of dengue were obtained through field studies that included passive facility-based fever surveillance, cost-of-illness surveys, serological surveys and healthcare utilisation surveys. All three sites conducted case detection using standardised procedures with uniform laboratory assays to diagnose dengue. Healthcare utilisation surveys were conducted to adjust population denominators in incidence calculations for differing healthcare seeking patterns. The fever surveillance data will allow calculation of age-specific incidence rates and comparison of symptomatic presentation between patients with dengue and non-dengue using multivariable logistic regression. Serological surveys assessed changes in immune status of cohorts of approximately 3000 randomly selected residents at each site at 6-month intervals. The age-stratified serosurvey data will allow calculation of seroprevalence and force of infection of dengue. Cost-of-illness evaluations were conducted among patients with acute dengue by Rapid Diagnostic Test.

Ethics and dissemination

By standardising methods to evaluate dengue burden across several sites in Africa, these studies will generate evidence for dengue burden in Africa and data will be disseminated as publication in peer-review journals in 2018.
‘I did try and point out about his dignity’: a qualitative narrative study of patients and carers’ experiences and expectations of junior doctors
Authors: Kostov Camille E , Rees Charlotte E , Gormley Gerard J , Monrouxe Lynn V
Published: January 2018

Objectives

For many years, the voice of patients has been understood as a critical element for the improvement of care quality in healthcare settings. How well medical graduates are prepared for clinical practice is an important question, but one that has rarely been considered from patient and public perspectives. We aimed to fill this gap by exploring patients and carers’ experiences and expectations of junior doctors.

Design

This comprises part of a wider study on UK medical graduates’ preparedness for practice. A qualitative narrative methodology was used, comprising four individual and six group interviews.

Participants

25 patients and carers from three UK countries.

Analysis

Data were transcribed, anonymised and analysed using framework analysis.

Main results

We identified three themes pertinent to answering our research question: (1) sources of knowledge (sources of information contributing to patients and carers’ perceptions of junior doctors’ impacting on expectations); (2) desires for student/trainee learning (experiences and expectations of medical training); and (3) future doctors (experiences and expectations of junior doctors). We also highlight metaphorical talk and humour, where relevant, in the quotes presented to give deeper insights into participants’ perspectives of the issues. Participants focused on personal and interpersonal aspects of being a doctor, such as respect and communication. There was a strong assertion that medical graduates needed to gain direct experience with a diverse range of patients to encourage individualised care. Participants narrated their experiences of having symptoms ignored and attributed to an existing diagnosis (‘diagnostic overshadowing’) and problems relating to confidentiality.

Conclusions

Our findings support the view that patients and carers have clear expectations about junior doctors, and that patient views are important for preparing junior doctors for practice. There is a necessity for greater dialogue between patients, doctors and educators to clarify expectations and confidentiality issues around patient care.
Study protocol for One Health data collections, analyses and intervention of the Sino-Swedish integrated multisectoral partnership for antibiotic resistance containment (IMPACT)
Authors: Sun Qiang , Wang Yang , Hulth Anette , Xiao Yonghong , Nilsson Lennart E , Li Xuewen , Bi Zhenwang , Liu Yuqing , Yin Hong , Luo Yanbo , Nilsson Maud , Sun Chengtao , Zhu Yiqing , Zheng Beiwen , Chen Baoli , Sun Pan , Ding Lilu , Xia Xi , Ottoson Jakob , Löfmark Sonja , Dyar Oliver James , Börjesson Stefan , Lundborg Cecilia Stalsby
Published: January 2018

Introduction

To effectively minimise the emergence and dissemination of antibiotic resistant bacteria, a holistic One Health approach is called for. The Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance Containment is a cross-sectoral and integrated project on antibiotic resistance, conducted in Shandong Province in China. This paper outlines the overall study protocol for the project. To our knowledge, this is the first research programme aiming to take a true holistic approach across multiple sectors simultaneously in China, and the first to incorporate both antibiotic use and infection prevention and control in addition to antibiotic resistance patterns. The project aims to address gaps in current knowledge and seeks to improve the situation through a system-wide intervention. By using a One Health approach we can address important research questions that individual discipline investigations are unable to. The results obtained should thus more closely reflect the world in which human health, animal health and the environment are inextricably and intimately interlinked.

Methods and analysis

Both quantitative and qualitative studies are included for households from 12 villages, their surrounding environment and a tertiary care hospital in a nearby town. The studies include analyses of antibiotic consumption for humans and pigs; qualitative and quantitative data on perceptions, knowledge and attitudes; faecal carriage of extended spectrum β-lactamase and carbapenemase-producingEnterobacteriaceaefrom pigs and humans, and occurrence in household drinking water, surface water, waste water and clinical bacterial isolates from the hospital. Carriage of methicillin-resistantStaphylococcus aureusin humans, household pigs and clinical bacterial isolates is also investigated. Furthermore, potential inter-relationships between these sources are analysed. A multifaceted One Health intervention is designed and implemented in 6 of the 12 villages. Repeated and continuous data collections take place over 2 years, where the repeated data collection is performed after 1 year of intervention. Comparisons are made between intervention and control villages, before and after the intervention.

Ethics

Ethics approval was obtained from the first Affiliated Hospital, College of Medicine, Zhejiang University, China, reference number 2015#185 and 2015#283.
Qualitative findings on building a partnered approach to implementation of a group-based diabetes intervention in VA primary care
Authors: Arney Jennifer , Thurman Kimberly , Jones Lindsey , Kiefer Lea , Hundt Natalie E , Naik Aanand D , Woodard LeChauncy D
Published: January 2018

Objective

Conduct a formative evaluation to inform the implementation of ‘Empowering Patients in Chronic Care’ (EPIC), an evidence-based interdisciplinary group medical appointment intervention to improve collaborative goal-setting in patients with treated but uncontrolled diabetes.

Design

The formative evaluation involved qualitative, in-depth interviews with clinicians, structured according to the Promoting Action on Research in Health Services framework. Interviews elicited (1) participants’ knowledge regarding interdisciplinary group self-management and goal-setting programmes and how well clinicians embrace these interventions (evidence), (2) physical and social climate at each target facility and how the intervention can best be embedded into routine primary care (context) and (3) site-specific needs to be addressed by our implementation team and clinicians’ preparedness and intentions to participate in the intervention (facilitation).

Setting

Clinicians were part of a primary care setting at one of five participating medical facilities within one Veterans Health Administration Veterans Affairs regional network.

Participants

We interviewed a snowball sample of 35 interdisciplinary clinicians engaged in diabetes management, practising leadership and administrators at target sites.

Results

Most participants had previous experience with diabetes group self-management programmes and viewed group appointments as an effective approach to enhancing care. Discussions about existing group appointments provided a context for evaluating potential barriers and facilitators to implementing EPIC into target sites. Interviews revealed clinicians’ expectations about the roles they would play in the intervention, their assessments of the roles and strategies to facilitate their performance in those roles.

Conclusions

Successful implementation of evidence-based practices into routine care requires a partnered approach with engaged local staff. The intervention should address local goals and research objectives to encourage bidirectional engagement. Robust partnerships are nurtured further by sustained, open communication and must consider the context, target population and local experience to address barriers and facilitators to implementation.
The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer
Authors: Nicholson Brian D , Oke Jason , Friedemann Smith Claire , Phillips Julie-Ann , Lee Jennifer , Abel Lucy , Kelly Sadie , Gould Isabella , Mackay Toni , Kaveney Zoe , Anthony Suzie , Hayles Shelley , Lasserson Daniel , Gleeson Fergus
Published: January 2018

Introduction

Cancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of ‘low-risk but not no-risk’ cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England’s cancer survival rates through establishing effective routes to early diagnosis.

Methods and analysis

To evaluate SCAN, we are collating a prospective database of patients referred onto the pathway by their general practitioner (GP). Patients aged over 40 years, with non-specific symptoms such as weight loss or fatigue, who do not meet urgent cancer referral criteria or for whom symptom causation remains unclear after investigation via other existing pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory testing and clinic review within 2 weeks. We will follow all patients in the primary and secondary care record for at least 2 years. The data will be used to understand the diagnostic yield of the SCAN pathway in the short term (28 days) and the long term (2 years). Routinely collected primary and secondary care data from patients not referred to SCAN but with similar symptoms will also be used to evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN to assess cost-effectiveness. Acceptability will be evaluated using patient and GP surveys.

Ethics and dissemination

The Oxford Joint Research Office Study Classification Group has judged this to be a service evaluation and so outside of research governance. The results of this project will be disseminated by peer-reviewed publication and presentation at conferences.
Time trends in peripheral artery disease incidence, prevalence and secondary preventive therapy: a cohort study in The Health Improvement Network in the UK
Authors: Cea-Soriano Lucía , Fowkes F Gerry R , Johansson Saga , Allum Alaster M , García Rodriguez Luis Alberto
Published: January 2018

Objectives

To assess time trends in symptomatic peripheral artery disease (PAD) incidence and prevalence, and secondary preventive therapy.

Design

Cohort study using The Health Improvement Network.

Setting

UK primary care.

Participants

Individuals aged 50–89 years identified annually between 2000 and 2014. Participants with symptomatic PAD were identified using Read codes.

Outcome measures

Incidence and prevalence of symptomatic PAD from 2000 to 2014, overall and by sex and age. Proportion of patients prescribed secondary preventive therapy with acetylsalicylic acid (ASA), clopidogrel, an ACE inhibitor, an angiotensin receptor blocker (ARB) and/or a statin.

Results

The incidence of symptomatic PAD per 10 000 person-years decreased over time, from 38.6 (men: 51.0; women: 28.7) in 2000 to 17.3 (men: 23.1; women: 12.4) in 2014. The prevalence of symptomatic PAD decreased from 3.4% (men: 4.5%; women: 2.5%) in 2000 to 2.4% (men: 3.1%; women: 1.7%) in 2014. Incidence and prevalence decreases were observed in all age groups. The proportions of patients prescribed ASA monotherapy, clopidogrel monotherapy and dual antiplatelet therapy in the 2 months after PAD diagnosis were 42.7%, 2.9% and 2.5%, respectively, during 2000–2003, and 44.7%, 11.0% and 5.2%, respectively, during 2012–2014. For ACE inhibitor/ARB therapy and statins, proportions in the 2 months after diagnosis were 30.2% and 31.2%, respectively, during 2000–2003, and 45.1% and 65.9%, respectively, during 2012–2014.

Conclusion

The incidence and prevalence of symptomatic PAD diagnosed in UK primary care are decreasing. A large proportion of the population with PAD in clinical practice does not receive guideline-recommended secondary prevention therapy.
Incidence and mortality of fractures by frailty level over 80 years of age: cohort study using UK electronic health records
Authors: Ravindrarajah Rathi , Hazra Nisha C , Charlton Judith , Jackson Stephen H D , Dregan Alex , Gulliford Martin C
Published: January 2018

Objective

This study aimed to estimate the association of frailty with incidence and mortality of fractures at different sites in people aged over 80 years.

Design

Cohort study.

Setting

UK family practices from 2001 to 2014.

Participants

265 195 registered participants aged 80 years and older.

Measurements

Frailty status classified into ‘fit’, ‘mild’, ‘moderate’ and ‘severe’ frailty. Fractures, classified into non-fragility and fragility, including fractures of femur, pelvis, shoulder and upper arm, and forearm/wrist. Incidence of fracture, and mortality within 90 days and 1 year, were estimated.

Results

There were 28 643 fractures including: non-fragility fractures, 9101; femur, 12 501; pelvis, 2172; shoulder and upper arm, 4965; and forearm/wrist, 6315. The incidence of each fracture type was higher in women and increased with frailty category (femur, severe frailty compared with ‘fit’, incidence rate ratio (IRR) 2.4, 95% CI 2.3 to 2.6). Fractures of the femur (95–99 years compared with 80–84 years, IRR 2.7, 95% CI 2.6 to 2.9) and pelvis (IRR 2.9, 95% CI 2.5 to 3.3) were strongly associated with age but non-fragility and forearm fractures were not. Mortality within 90 days was greatest for femur fracture (adjusted HR, compared with forearm fracture 4.3, 95% CI 3.7 to 5.1). Mortality was higher in men and increased with age (HR 5.3, 95% CI 4.3 to 6.5 in those over 100 years compared with 80–84 years) but was less strongly associated with frailty category. Similar associations with fractures were seen at 1-year mortality.

Conclusions

The incidence of fractures at all sites was higher in women and strongly associated with advancing frailty status, while the risk of mortality after a fracture was greater in men and was associated with age rather than frailty category.
Impact of maternal common mental disorders on child educational outcomes at 7 and 9 years: a population-based cohort study in Ethiopia
Authors: Mekonnen Habtamu , Medhin Girmay , Tomlinson Mark , Alem Atalay , Prince Martin , Hanlon Charlotte
Published: January 2018

Objectives

To examine the association between exposure to maternal common mental disorders (CMD) in preschool and early school age children and subsequent child educational outcomes.

Design

A population-based cohort study.

Setting

The study was undertaken in the Butajira health and demographic surveillance site (HDSS), a predominantly rural area of south central Ethiopia.

Participants

Inclusion criteria are women aged between 15 and 49 years, able to speak Amharic, in the third trimester of pregnancy and resident of the HDSS. 1065 women were recruited between July 2005 and February 2006 and followed up. When the average age of children was 6.5 years old, the cohort was expanded to include an additional 1345 mothers and children who had been born in the 12 months preceding and following the recruitment of the original cohort, identified from the HDSS records. Data from a total of 2090 mother–child dyads were included in the current analysis.

Measures

Maternal CMD was measured when the children were 6–7 (6/7) and 7–8 (7/8) years old using the Self-reporting Questionnaire, validated for the setting. Educational outcomes (dropout) of the children at aged 7/8 years (end of 2013/2014 academic year) were obtained from maternal report. At age 8/9 years (end of 2014/2015 academic year), educational outcomes (academic achievement, absenteeism and dropout) of the children were obtained from school records.

Results

After adjusting for potential confounders, exposure to maternal CMD at 7/8 years was associated significantly with school dropout (OR 1.07; 95% CI 1.00 to 1.13, P=0.043) and absenteeism (incidence rate ratio 1.01; 95% CI 1.00 to 1.02 P=0.026) at the end of 2014/2015 academic year. There was no association between maternal CMD and child academic achievement.

Conclusion

Future studies are needed to evaluate whether interventions to improve maternal mental health can reduce child school absenteeism and dropout.
Inner-city green space and its association with body mass index and prevalent type 2 diabetes: a cross-sectional study in an urban German city
Authors: Müller Grit , Harhoff Roland , Rahe Corinna , Berger Klaus
Published: January 2018

Objective

The accessibility of green space is an important aspect of the urban residential environment and has been found to be beneficial for health and well-being. This study investigates the association between different indicators of green space and the outcomes body mass index (BMI) and prevalent type 2 diabetes in an urban population.

Design

Population-based cross-sectional study.

Setting

Dortmund, a city located in the industrial Ruhr area in Western Germany.

Participants

1312 participants aged 25–74 years from the Dortmund Health Study.

Methods

The participants’ addresses were geocoded and shapefiles of statistical districts, road network and land use, as well as data on neighbourhood characteristics were obtained at baseline. Three indicators of green space were constructed using geographical information systems: proportion of green space, recreation location quotient (RLQ) weighted by population and distance to the next park or forest. Multilevel linear and logistic regression analyses on the association of green space with BMI and type 2 diabetes were performed, adjusted by individual-level characteristics and neighbourhood unemployment rate.

Results

The multilevel regression analyses showed no association between green space and BMI. In contrast, the three indicators of green space were significantly associated with type 2 diabetes. Residents of neighbourhoods with a low RLQ had a 2.44 (95% CI 1.01 to 5.93) times higher odds to have type 2 diabetes compared with residents of high RLQ neighbourhoods. Likewise, residing more than 0.8 km away from the nearest park or forest increased the odds of type 2 diabetes (OR 1.71, 95% CI 1.05 to 2.77).

Conclusions

This study indicates that green space and its spatial accessibility might play a role in the development of type 2 diabetes. Further research is needed to clarify this association.
Monitoring intensive care unit performance—impact of a novel individualised performance scorecard in critical care medicine: a mixed-methods study protocol
Authors: Fernando Shannon M , Neilipovitz David , Sarti Aimee J , Rosenberg Erin , Ishaq Rabia , Thornton Mary , Kim John
Published: January 2018

Introduction

Patients admitted to a critical care medicine (CCM) environment, including an intensive care unit (ICU), are susceptible to harm and significant resource utilisation. Therefore, a strategy to optimise provider performance is required. Performance scorecards are used by institutions for the purposes of driving quality improvement. There is no widely accepted or standardised scorecard that has been used for overall CCM performance. We aim to improve quality of care, patient safety and patient/family experience in CCM practice through the utilisation of a standardised, repeatable and multidimensional performance scorecard, designed to provide a continuous review of ICU physician and nurse practice, as well as departmental metrics.

Methods and analysis

This will be a mixed-methods, controlled before and after study to assess the impact of a CCM-specific quality scorecard. Scorecard metrics were developed through expert consensus and existing literature. The study will include 19 attending CCM physicians and approximately 300 CCM nurses. Patient data for scorecard compilation are collected daily from bedside flow sheets. Preintervention baseline data will be collected for 6 months for each participant. After this, each participant will receive their scorecard measures. Following a 3-month washout period, postintervention data will be collected for 6 months. The primary outcome will be change in performance metrics following the provision of scorecard feedback to subjects. A cost analysis will also be performed, with the purpose of comparing total ICU costs prior to implementation of the scorecard with total ICU costs following implementation of the scorecard. The qualitative portion will include interviews with participants following the intervention phase. Interviews will be analysed in order to identify recurrent themes and subthemes, for the purposes of driving scorecard improvement.

Ethics and dissemination

This protocol has been approved by the local research ethics board. Publication of results is anticipated in 2019. If this intervention is found to improve patient- and unit-directed outcomes, with evidence of cost-effectiveness, it would support the utilisation of such a scorecard as a quality standard in CCM.
Understanding the use of email consultation in primary care using a retrospective observational study with data of Dutch electronic health records
Authors: Huygens Martine W J , Swinkels Ilse C S , Verheij Robert A , Friele Roland D , van Schayck Onno C P , de Witte Luc P
Published: January 2018

Objectives

It is unclear why the use of email consultation is not more widespread in Dutch general practice, particularly because, since 2006, its costs can be reimbursed. To encourage further implementation, it is needed to understand the current use of email consultations. This study aims to understand the use of email consultation by different patient groups, compared with other general practice (GP) consultations.

Setting

For this retrospective observational study, we used Dutch routine electronic health record data obtained from NIVEL Primary Care Database for the years 2010 and 2014.

Participants

200 general practices were included in 2010 (734 122 registered patients) and 434 in 2014 (1 630 386 registered patients).

Primary outcome measures

The number and percentage of email consultations and patient characteristics (age, gender, neighbourhood socioeconomic status and diagnoses) of email consultation users were investigated and compared with those who had a telephone or face-to-face consultation. General practice characteristics were also taken into account.

Results

32.0% of the Dutch general practices had at least one email consultation in 2010, rising to 52.8% in 2014. In 2014, only 0.7% of the GP consultations were by email (the others comprised home visits, telephone and face-to-face consultations). Its use highly varied among general practices. Most email consultations were done for psychological (14.7%); endocrine, metabolic and nutritional (10.9%); and circulatory (10.7%) problems. These diagnosis categories appeared less frequently in telephone and face-to-face consultations. Patients who had an email consultation were older than patients who had a telephone or face-to-face consultation. In contrast, patients with diabetes who had an email consultation were younger.

Conclusion

Even though email consultation was done in half the general practices in the Netherlands in 2014, the actual use of it is extremely low. Patients who had an email consultation differ from those who had a telephone or face-to-face consultation. In addition, the use of email consultation by patients is dependent on its provision by GPs.
Determinants of non-adherence to treatment for tuberculosis in high-income and middle-income settings: a systematic review protocol
Authors: Wurie Fatima B , Cooper Vanessa , Horne Robert , Hayward Andrew C
Published: January 2018

Introduction

Treatment for tuberculosis (TB) is highly effective if taken according to prescribed schedules. However, many people have difficulty adhering to treatment which can lead to poorer clinical outcomes, the development of drug resistance, increased duration of infectivity and consequent onward transmission of infection. A range of approaches are available to support adherence but in order to target these effectively a better understanding of the predictors of poor adherence is needed. This review aims to highlight the personal, sociocultural and structural factors that may lead to poor adherence in high-income and middle-income settings.

Methods and analysis

Seven electronic databases, Medline, EMBASE, CINAHL, PsycInfo, The Cochrane Library, Scopus and Web of Science, will be searched for relevant articles using a prespecified search strategy. Observational studies will be targeted to explore factors that influence adherence to treatment in individuals diagnosed with TB. Screening title and abstract followed by full-text screening and critical appraisal will be conducted by two researchers. Data will be extracted using the Population, Exposure, Comparator, Outcomes, Study characteristics framework. For cross-study assessment of strength of evidence for particular risk factors affecting adherence we will use the Grading of Recommendations, Assessment, Development and Evaluation tool modified for prognostic studies. A narrative synthesis of the studies will be compiled. A meta-analysis will be considered if there are sufficient numbers of studies that are homogenous in study design, population and outcomes.

Dissemination

A draft conceptual framework will be identified that (A) identifies key barriers to adherence at each contextual level (eg, personal, sociocultural, health systems) and (B) maps the relationships, pathways and mechanisms of effect between these factors and adherence outcomes for people with TB. The draft conceptual framework will guide targeting of adherence interventions and further research.

PROSPERO registration number

CRD42017061049.